This application is a continuation of U.S. patent application Ser. No. 12/062,740, filed on which is a continuation of U.S. patent application Ser. No. 10/339,767 filed on Jan. 9, 2003, now U.S. Pat. No. 7,355,024, which claims priority to provisional applications: 60/388,315 filed on Jun. 14, 2002, provisional application 60/361,073 filed on Mar. 1, 2002 and provisional application 60/346,898 filed on Jan. 11, 2002, the contents of which are incorporated by reference.
REFERENCE TO SEQ ID The Sequence listing in “1247090060.tx” created on Aug. 1, 2011, being 108 KB in size, is incorporated by reference.
FIELD OF THE INVENTION The invention relates to the field of assays for the detection of factors that modulate gene expression. Specifically, the invention relates to reporter constructs and methods for identifying agents that modulate the expression of the INGAP gene.
BACKGROUND OF THE INVENTION Islet neogenesis gene associated protein (INGAP protein) has been identified as a pancreatic acinar cell protein that can induce islet cell neogenesis from progenitor cells resident in the pancreas in a manner that recapitulates islet development during normal embryogenesis. INGAP is unique in its ability to stimulate growth and differentiation of islets of Langerhans from precursor cells associated with pancreas. These islets evolve a mature insulin secretory profile capable of responding to perturbations in blood glucose in a physiologic manner. This potential anti-diabetic therapeutic has been shown to demonstrate homology across several species and to exert a biological response.
Pancreatic islet cell mass is lost in type 1 diabetes mellitus, a disease in which a progressive autoimmune reaction results in the selective destruction of insulin-producing β-cells. In type 2 diabetes mellitus, so-called adult-onset disease, but also increasingly a condition in young overweight people, the β-cell mass may be reduced by as much as 60% of normal. The number of functioning β-cells in the pancreas is of critical significance for the development, course, and outcome of diabetes. In type I diabetes, there is a reduction of β-cell mass to less than 2% of normal. Even in the face of severe insulin resistance as occurs in type II diabetes, the development of diabetes only occurs if there is inadequate compensatory increase in β-cell mass. Thus, the development of either of the major forms of diabetes can be regarded as a failure of adaptive β-cell growth and a subsequent deficiency in insulin secretion. Stimulating the growth of islets and β-cells from precursor cells, known as islet neogenesis, is an attractive approach to the amelioration of diabetes. There is need in the art for methods to identify agents that can modulate the expression of INGAP, whether in animals or in cultured cells.
BRIEF SUMMARY OF THE INVENTION It is an object of the invention to provide a reporter construct containing the 5′-regulatory region from mammalian INGAP gene.
It is another object of the invention to provide methods for identifying agents which modulate INGAP expression.
It is another object of the invention to provide a nucleic acid or fragment of INGAP 5′-regulatory region.
It is another object of the invention to provide methods for increasing INGAP expression.
It is another object of the invention to provide a kit for modulating INGAP expression.
These and other objects of the invention are provided by one or more of the embodiments described below.
In one aspect of the invention a reporter construct is provided. The reporter construct comprises a regulatory region nucleotide sequence and a nucleotide sequence encoding a detectable product. In one aspect of the invention, the reporter construct is provided in a vector. The regulatory region nucleotide sequence is linked to the nucleotide sequence encoding a detectable product. The regulatory region nucleotide sequence may comprise one or more fragments of 5′ regulatory region of the INGAP genomic sequence, SEQ ID NO: 23, or it may comprise the entire length of the 5′ regulatory region. In one embodiment of the reporter construct, a promoter element is interposed between the regulatory region nucleotide sequence and the nucleotide sequence encoding a detectable product. The promoter element may be selected from the promoter elements present in the INGAP regulatory sequence. Alternatively, the promoter element present in the vector comprising the reporter construct may be used. The detectable product encoded by the said nucleotide sequence encoding a detectable product could be either a nucleic acid or a protein. The detectable product need not be the INGAP gene nucleic acid or protein.
In another embodiment of the invention, a method identifying agents that modulate INGAP expression is provided. The method comprises contacting a cell with a test agent, wherein the cell comprises a reporter construct of the present invention. Expression of the detectable nucleic acid or protein product in the cell is determined. A test agent is identified as a modulator of INGAP expression if the test agent modulates expression of the detectable product in the cell.
In another embodiment of the invention, an isolated nucleic acid comprising the genomic sequence of the hamster INGAP gene (SEQ ID NO: 2), or a fragment thereof is provided.
According to another embodiment of the invention, an in vitro method for identifying agents that modulate INGAP expression is provided. The method comprises contacting a test agent with a reporter construct of the present invention in a cell-free system that allows for transcription and translation of a nucleotide sequence. Expression of the detectable product is determined. The substance is identified as a modulator of INGAP expression if the test substance modulates expression of the detectable product.
According to another embodiment of the invention, an in vitro method for identifying an agent that modulate INGAP expression is provided. The method comprises contacting a test agent with a nucleic acid of the invention. Binding of the test agent to the nucleic acid is determined. The test agent is identified as a modulator of INGAP expression if the test agent binds to the nucleic acid.
According to another embodiment of the invention a method for increasing INGAP expression is provided. An effective amount of a factor that stimulates INGAP expression directly or indirectly, for example cytokines, chemokines, growth factors, or pharmacological agents, is administered to a mammal in need of increased INGAP expression.
According to another embodiment of the invention a kit for modulating INGAP expression is provided. The kit comprises a modulator of INGAP expression and instructions for using the modulator of INGAP expression to modulate INGAP expression.
According to another embodiment of the invention a method for modulating INGAP expression in a mammal to treat a disease state related to reduced islet cell function is provided. The method comprises the step of administering to the mammal an effective amount of a modulator of INGAP expression whereby the level of INGAP expression in the mammal is modified.
All documents cited are, in relevant part, incorporated herein by reference; the citation of any document is not to be construed as an admission that it is prior art with respect to the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows the annotation of the hamster INGAP gene structure. The boundaries of introns 1-5 are listed in Table 1.
FIG. 2 shows an overview of the 5′-regulatory region of the hamster INGAP gene (nucleotides 1-3137 of SEQ ID NO: 2) showing many well known and well-characterized transcription factor binding sites. The minimal promoter element contains the regions noted with an underline (CAAT-box, TATA-box, and GC-box).
FIG. 3 shows a schematic of many well known and well-characterized transcription factor-binding sites for nucleotides 1-3123 of the 5′-regulatory region (SEQ ID NO: 1) of the hamster INGAP gene. Table 3 further describes these transcription factor-binding sites.
FIG. 4 shows the predicted transcription start sites within the 5′-regulatory region (SEQ ID NO: 1) of the hamster INGAP gene (SEQ ID NO: 2). The predicted start site is indicated by a boldface nucleotide. The start and end nucleotide numbers are indicated for the promoter sequence. The numbers refer to nucleotide numbers of the hamster INGAP gene (SEQ ID NO: 2)
FIG. 5 shows the adapter primer structure and sequence used in gene walking. Adapter primer 1 (AP1) and adapter primer 2 (AP2) are shown.
FIGS. 6 and 7 show the strategy for reconstructing the hamster INGAP gene. The hamster INGAP gene was reconstructed using the technique of gene walking. Shown are the fragments and the gene specific primers (GSP1 and GSP2) used in PCR amplification for gene walking. Fragments were joined together using unique restriction enzyme sites within each fragment. The nucleotide sequences of the individual primers are listed in Table 2.
FIG. 8 shows the fragments of INGAP 5′-regulatory region, which were cloned into pβGal-basic upstream of a β-galactosidase reporter gene. The labels on the left refer to the nucleotide fragments of SEQ ID NO: 23 which were cloned upstream of pβGal-basic.
FIG. 9A shows reporter activity in human embryonic kidney cells (293T) transfected with a reporter construct that contains various fragments of the 5′-regulatory region (SEQ ID NO: 23) of hamster INGAP DNA cloned upstream of a β-galactosidase reporter gene (pβGal-basic), or in a reporter construct which contains no INGAP DNA. The cells are stimulated with phorbol myristate acetate. Promoter activity is assessed by determining the level of β-galactosidase present in the cell using a β-galactosidase luminescent assay.
FIG. 9B shows reporter activity in human embryonic kidney cells (293T) transfected with a reporter construct that contains nucleotides 2030 to 3137 of the 5′-regulatory region (SEQ ID NO: 23) of hamster INGAP cloned upstream of a β-galactosidase reporter gene, or in a reporter construct which contains no INGAP DNA. The cells are stimulated with leukemia inhibitory factor. Promoter activity is assessed by determining the level of β-galactosidase present in the cell using a β-galactosidase luminescent assay.
FIG. 10 shows the reporter activity in human embryonic kidney cells (293T) transfected with a reporter construct that contains different fragments (see FIG. 8) of the 5′-regulatory region of hamster INGAP cloned upstream of a β-galactosidase reporter gene. The cells are stimulated with phorbol myristate acetate. Concentrations of PMA used are 6 ng/ml, 17 ng/ml, 50 ng/ml, 100 ng/ml, or 300 ng/ml. Promoter activity is assessed by determining the level of β-galactosidase present in the cell using a β-galactosidase luminescent assay.
FIG. 11 shows reporter activity in human embryonic kidney cells (293T) transfected with a reporter construct that contains different fragments (see FIG. 8) of the 5′-regulatory region of hamster INGAP cloned upstream of a β-galactosidase reporter gene. The cells are stimulated with human leukemia inhibitory factor (hLIF). Concentrations of hLIF used are 1 ng/ml, 10 ng/ml, or 30 ng/ml. Promoter activity was assessed by determining the level of β-galactosidase present in the cell using a β-galactosidase luminescent assay.
FIG. 12 shows RNA analysis for INGAP gene upregulation in rat amphicrine pancreatic cells, AR42J, treated with cytokine IL-6 or untreated. Total RNA is probed by Northern analysis for INGAP gene.
DETAILED DESCRIPTION OF THE INVENTION Definitions It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise.
The term “promoter” is used to define the region of a gene at which initiation and rate of transcription are controlled. It contains the site at which RNA polymerase binds and also sites for the binding of regulatory proteins, e.g. transcription factors, repressors, etc. In order to differentiate between the transcription initiation site and other sites that modulate rate of transcription, promoter region is generally subdivided into “minimal promoter element” and “regulatory region”. The term “minimal promoter element” or sometimes simply referred to as “promoter” therefore may include TATA box, GC-rich sequence and CAAT box; while “regulatory region” is usually a long stretch of nucleotide sequence where transcription factors and other factors bind. Most eukaryotic genes have long regulatory regions where many different transcription factors bind. The expression or the lack of expression of a given gene in a given cell type, tissue, organ, or an organism is governed by the interactions that take place on its regulatory region.
The term “transcription factor” is used to describe the proteins that bind short stretches of DNA in the regulatory regions of a gene. Transcription factors may interact with each other as well as RNA polymerase. Thus, transcription factors may bind hormones or second messengers, DNA, RNA, other transcription factors, or other proteins. They may activate or inhibit transcription of a given gene. Transcription factors are also sometimes referred to as “enhancers” or “repressors”. Transcription factor binding sites can be used to identify agents that bind to the 5′-regulatory region of the gene and modulate the gene's expression.
The term “reporter” is used to describe a coding sequence attached to a heterologous promoter or enhancer elements and whose product, either nucleic acid or protein, is easily detected and is quantifiable. Some common reporter genes include β-galactosidase (lacZ), chloramphenicol acetyltransferase (cat), β-glucuronidase (GUS), and green fluorescent protein (GFP).
A “reporter construct” is a piece of nucleic acid that includes a promoter element and a reporter gene housed in a suitable vector plasmid DNA. Regulatory region nucleotide sequences may be cloned 5′ of the promoter element to determine if they contain transcription factor binding sites. The reporter construct-containing vector is introduced into a cell that contains many transcription factors. Activation of the reporter gene by transcription factors may be monitored by detection and quantification of the product of the reporter gene.
The term “agent” is used here to essentially describe any means to modulate INGAP expression. Agent may be a chemical compound, a biological agent, or a physical force, a mechanical contraption, or any combinations thereof.
INGAP Promoter and Regulatory Region It is a discovery of the present inventors that INGAP gene is regulated by a 5′-regulatory region that is susceptible to modulation by many known transcription factors, including PMA and LIF.
It is a further discovery of the present invention that the 5′-regulatory region nucleotide sequence of the INGAP gene may be used in screening assays to identify agents capable of modulating the INGAP gene expression. These modulating agents have potential as therapeutic agents for treating pathological conditions including, but not limited to, diabetes mellitus, both type 1 and type 2, endocrine and non-endocrine hypoplasia, hypertrophy, adenoma, neoplasia, and nesidioblastosis.
Mammalian INGAP, like most genes, has a 5′-regulatory region followed by introns and exons. The sequence of a mammalian (Hamster sp.) INGAP gene is provided as SEQ ID NO: 2. FIG. 1 details the relative location of the 5′-regulatory region, the introns and the exons of the hamster INGAP gene. The boundaries of introns 1-5 and the location of the TATA-box and the poly-A signal are listed in Table 1.
TABLE 1
Position In INGAP
Description Gene (SEQ ID NO: 2)
TATA-Box 3094
INTRON 1 3150-3426
INTRON 2 3508-4442
INTRON 3 4562-4735
INTRON 4 4874-5459
INTRON 5 5587-5843
Poly-A Signal 6098-6103
The nucleotide sequence of the 5′-regulatory region including the promoter elements of mammalian INGAP, is shown partially in SEQ ID NO: 1, and completely in SEQ ID NO: 2 and 23 (nucleotides 1-3137 of SEQ ID NO: 2). Nucleotides 1-3120 of SEQ ID NO: 1 are identical to nucleotides 1-3120 of SEQ ID NO: 2 and SEQ ID NO: 23. An overview of the 5′-regulatory region is shown in FIG. 2. Representative transcription enhancer/repressor binding sites are shown also in FIG. 2. Predicted transcription enhancer/repressor binding sites for nucleotides 1-3123 of the 5′-regulatory region are shown in FIG. 3. Table 3 at the end of the specification details these transcription factors and their binding sites, and their locations in the regulatory region. Potential transcription factor binding analysis was done using MatInspector Professional™, which is a bioinformatics software that utilizes a library of matrix descriptions for transcription factor binding sites to locate matches in sequences of unlimited length (Quandt, K., Frech, K., Karas, H., Wingender, E., Werner, T. (1995) Nucleic Acids Res. 23, 4878-4884).
Table 3 lists predicted binding proteins (Further Information) based upon their classification into functionally similar matrix families (Family/matrix). The DNA sequence predicted to bind the protein (Sequence), whether sense or antisense DNA (Str) and location of the sequence in SEQ ID NO: 2, (Position) are listed. Further the similarity to the consecutive highest conserved nucleotides of a matrix (Core sim.) and similarity to all nucleotides in that matrix (Matrix sim.) along with the optimized value (Opt) defined in a way that a minimum number of matches is found in non-regulatory test sequences are also listed. Details to the algorithms used in MatInspector Professional™ is referenced:
OPT: This matrix similarity is the optimized value defined in a way that a minimum number of matches are found in non-regulatory test sequences (i.e. with this matrix similarity the number of false positive matches is minimized). This matrix similarity is used when the user checks “Optimized” as the matrix similarity threshold for MatInspector Professional™.
Family: Each matrix belongs to a so-called matrix family, where functionally similar matrices are grouped together, eliminating redundant matches by MatInspector Professional™ professional (if the family option was selected). E.g. the matrix family V$NFKB includes 5 similar matrices for NFkappaB (V$NFKAPPAB.01, V$NFKAPPAB 0.02, V$NFKAPPAB 0.03, V$NFKAPPAB50.01, V$NFKAPPAB65.01) as well as 1 matrix for the NFkappaB related factor c-Rel (V$CREL.01).
Matrix: The MatInspector Professional™ matrices have an identifier that indicates one of the following seven groups: vertebrates (V$), insects (I$), plants (P$), fungi (F$), nematodes (N$), bacteria (B$), and other functional elements (O$); followed by an acronym for the factor the matrix refers to, and a consecutive number discriminating between different matrices for the same factor. Thus, V$OCT1.02 indicates the second matrix for vertebral Oct-1 factor.
Core Sim: The “core sequence” of a matrix is defined as the (usually 4) consecutive highest conserved positions of the matrix. The core similarity is calculated as described here. The maximum core similarity of 1.0 is only reached when the highest conserved bases of a matrix match exactly in the sequence. More important than the core similarity is the matrix similarity which takes into account all bases over the whole matrix length.
Matrix Sim: The matrix similarity is calculated as described here. A perfect match to the matrix gets a score of 1.00 (each sequence position corresponds to the highest conserved nucleotide at that position in the matrix), a “good” match to the matrix usually has a similarity of >0.80. Mismatches in highly conserved positions of the matrix decrease the matrix similarity more than mismatches in less conserved regions.
Another aspect of the invention provides for a reporter construct. Reporter constructs contain a 5′ regulatory region nucleotide sequence fragment of SEQ ID NO: 23 (e.g., an enhancer and/or repressor binding site containing region), a promoter element (which may or may not be from INGAP regulatory region nucleotide sequence, SEQ ID NO: 23), and a reporter gene. The 5′-regulatory region nucleotide sequence is positioned upstream of the reporter gene. In order to determine the identity of various transcription factors that bind the 5′ regulatory region nucleotide sequence and to elucidate their binding locations within the 5′ regulatory nucleotide sequence of the INGAP gene, the region may be mapped using deletion analysis. One or more fragments of the regulatory region nucleotide sequence may be initially analyzed for their responses to various transcription factor activators. Once, a region of interest is determined, further fine mapping may be carried out where DNA from different locations within the regulatory region could be combined to make a more robust, and responsive reporter construct. DNA sequences, such as INGAP 5′-regulatory region DNA or a fragment thereof, can be manipulated by methods well known in the art. Examples of such techniques include, but are not limited to, polymerase chain reaction (PCR), restriction enzyme endonuclease digestion, ligation, and gene walking. Cloning fragments of DNA, such as 5′-regulatory regions is well known in the art.
Another approach to quantify the expression levels of a gene is to measure transcription of the gene. PCR-ELISA may be used to capture transcripts onto a solid phase using biotin or digoxigenin-labelled primers, oligonucleotide probes (oligoprobes) or directly after incorporation of the digoxigenin into the transcripts (Watzinger, F. and Lion, T. (2001) Nucleic Acids Res., 29, e52). Once captured, the transcripts can be detected using an enzyme-labeled avidin or anti-digoxigenin reporter molecule similar to a standard ELISA format. Another approach is to employ real-time PCR to detect the transcript of the reporter gene (Mackay, I. M. and Nitsche, A., Nucleic Acids Res. 2002 Mar. 15; 30 (6), 1292-305). In real-time PCR fluorogenic nucleotides are used and progress of the transcript is monitored in real-time as the polymerase transcribes the reporter gene.
The promoter element in the reporter construct may or may not be from the same gene as the 5′-regulatory region. As an example, the enhancer/repressor region from the INGAP 5′-regulatory region, or a fragment of the enhancer/repressor region from the INGAP 5′-regulatory region, may be cloned upstream of a heterologous minimal promoter element, e.g., the minimal CMV promoter (Boshart et al., 1985) and the promoters for TK (Nordeen, 1988), IL-2, and MMTV.
Transcription of a gene begins around the minimal promoter. FIG. 4 shows the predicted transcription start sites for mammalian INGAP gene (SEQ ID NO: 2). SEQ ID NO: 2 was analyzed using “Neural Network Promoter Prediction” program designed by Martin Reese to identify eukaryotic promoter recognition elements such as TATA-box, GC-box, CAAT-box, and the transcription start site. These promoter elements are present in various combinations separated by various distances in sequence. The program is available on the Internet and is located at http://www.fruitfly.org/seq_tools/promoter.html.
The reporter construct can be used to identify agents that modulate, either alone or in combination, the expression of INGAP. Some such agents may modulate expression of INGAP by binding to the regulatory region directly while others may regulate expression of transcription factors that bind to the INGAP regulatory region.
The reporter construct can be transfected into a host cell in vitro, or in vivo through the pancreatic duct, either transiently or stably, and a test agent introduced to the assay system. Examples of test agents include, but are not limited to organic and inorganic chemical agents, carbohydrates, proteins, oligonucleotides, cholecystokinin, mechanically induced pressure, and agents which cause a pancreatic duct obstruction. Expression of the reporter gene product can be determined by an assay appropriate for the reporter gene employed. Examples of such assays include, but are not limited to a luminescent assay for β-galactosidase or luciferase, an enzymatic assay for chloramphenicol acetyl transferase, and fluorescence detection for fluorescent proteins. Such assays are well known in the art, and a skilled artisan will be able to select an appropriate assay for the chosen reporter. A test agent is identified as a modulator of INGAP expression if the test agent modulates expression of the reporter gene product. Preferably the level of increase or decrease is at least 50%, 100%, 200%, 500%, or 1000%, but any statistically significant change can be an indicator of modulatory activity. A skilled artisan may also determine reporter gene product expression in untreated cells, and in treated and untreated cells transfected with a promoter-less reporter gene only. Such determinations can be used to determine background levels of expression.
Test agents can also be obtained by fractionating pancreatic secretion fluids. A pancreatic duct obstruction can be used as an exemplary method of harvesting pancreatic secretion fluids. The pancreatic secretion fluids can be fractionated by methods well known in the art. Examples include high-pressure liquid chromatography (HPLC), size exclusion chromatography, hydrophobic interacting columns, and density gradient centrifugation. Individual fractions can be tested for agents that modulate reporter gene expression using a method described herein. The individual fractions can be further fractionated to identify agents that modulate reporter gene expression. The identified test agents can be used to modulate the expression of INGAP.
A host cell can be any cell suitable for transfection and maintenance in a suitable assay system. Examples of suitable cells include, but are not limited to, mammalian cells, human cells, mouse cells, rat cells, monkey cells, dog cells, bovine cells, and porcine cells. Preferably the cells used will be human cells. The cells could be either transformed cells line or primary cells. Whole organ explants may also be used where the regulation may be monitored over many different cell types. Many methods exist in the art for transfecting or infecting cells with reporter construct DNA. Such methods include, but are not limited to, lipofection, electroporation, calcium phosphate precipitation, DEAE dextran, gene guns, and modified viral techniques (e.g., recombinant adenovirus or recombinant retrovirus). The skilled artisan can readily choose a method suitable for use with a given cell type and assay system.
The reporter construct can also be introduced in vivo directly into cells of the pancreas. Examples of methods to introduce the reporter construct into pancreatic cells in vivo include pancreatic duct retrograde perfusion and in vivo electroporation (Mir, 2001). The reporter construct encodes a reporter gene product that is readily measured in vivo. A test agent can be administered systemically or locally, and expression of the reporter gene in vivo can be determined by an assay appropriate for the particular reporter employed. Examples of such include a fluorescence assay for green fluorescent protein.
Methods for identifying agents that modulate INGAP expression can also be accomplished in vitro. The reporter construct can be contacted with a test agent in vitro under conditions sufficient for transcription and/or translation of the reporter gene. Components such as rabbit reticulocyte lysates or wheat germ extracts can be utilized for such a method. Subsequently, the expression level of the reporter gene can be determined as described above utilizing an appropriate assay for a given reporter gene. A test agent is identified as a modulator of INGAP expression if the test agent modulates expression of the reporter gene. Threshold levels of change can be set by the practitioner as discussed above.
A test agent can alternatively be contacted with an isolated and purified INGAP 5′-regulatory DNA molecule and one can determine if the test agent binds to the DNA molecule. Test agents can be a chemical agent, a protein, or a nucleic acid. Appropriate INGAP 5′-regulatory DNA molecules would include nucleotides 1-6586 of SEQ ID NO: 2, the 5′-regulatory region DNA (SEQ ID NO: 1, or SEQ ID NO: 23), or any fragment of the 5′-regulatory region, preferably a fragment which contains one or more enhancer/repressor binding sites. Methods to determine binding of the test agent to the fragment of DNA are well known in the art, e.g., electrophoretic mobility shift assay (EMSA). See for example Sambrook et al., MOLECULAR CLONING: A LABORATORY MANUAL, 2d ed., 1989, at pages 9.50-9.51. Fragments of the 5′-regulatory region can be obtained by methods well known in the art using the disclosed sequence (SEQ ID NO: 2). Examples of such methods include, PCR, restriction enzyme digestion, and chemical synthesis. Any fragment of DNA within the 5′-regulatory region (SEQ ID NO: 1, or 23) can be used. The exact location that an agent binds can be determined for example by utilizing smaller fragments to map precisely the binding site for the test agent. Test agents that bind in the assay can be further tested in other assays that require modulatory activity.
An agent that causes an increase or decrease in reporter gene expression can be used as a modulator of INGAP expression. The modulator can be administered to a mammal in need of such modulation. Examples of mammals that may need INGAP expression modulation are those with reduced pancreatic function, in particular reduced islet cell function. Such mammals include those who have diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, hyperglycemia, obesity, and pancreatic insufficiency.
An agent that is identified as a modulator of INGAP expression can be supplied in a kit to treat diseases associated with reduced islet cell function. The kit would comprise in single or divided containers, in single or divided doses a modulator of INGAP expression. Written instructions may be included for using the modulator of INGAP expression. The instructions may simply refer a reader to another location such as a website or other information source.
Agents that cause an increase in reporter gene expression can be used to increase INGAP expression to treat a disease state related to reduced islet cell function. Agents that cause a decrease in reporter gene expression can be used to decrease INGAP expression to treat a disease state related to hyperactivity of islet cells or a disease where reduced INGAP expression is desirable. Examples of such agents include, but are not limited to, PMA, LIF, interleukin-6, Oncostatin M, and ciliary neurotropic factor. Agents can be administered by any number of routes including, but not limited to, oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, transdermal, subcutaneous, intraperitoneal, intranasal, parenteral, topical, sublingual, rectal, or pancreatic duct retrograde perfusion. Agents for oral administration can be formulated using pharmaceutically acceptable carriers well known in the art in dosages suitable for oral administration. Such carriers enable the pharmaceutical compositions to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for ingestion by the mammal.
Agents for intravenous, intramuscular, intra-arterial, transdermal, and subcutaneous injections can be formulated using pharmaceutically acceptable carriers well known in the art in dosages suitable for injection into the mammal. Agents for intranasal, topical, and rectal administration can be formulated using pharmaceutically acceptable carriers well known in the art in dosages suitable for surface administration to the mammal. Mammals in need of an increase in INGAP expression include for example, mammals with diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, hyperglycemia, obesity, and pancreatic insufficiency. Mammals in need of a decrease in INGAP expression include for example, mammals with hypoglycemia.
The following examples are offered by way of illustration and do not limit the invention disclosed herein.
EXAMPLES Example 1 Hamster INGAP Genomic Sequence and Structure The hamster INGAP genomic sequence and structure was determined by gene walking (Clontech) and DNA sequencing. Gene walking is a method for walking upstream toward a promoter or downstream in genomic DNA from a known sequence, such as cDNA. This method utilizes four uncloned, adapter-ligated genomic fragment libraries. The manufacturer's recommended protocol is followed with one notable exception; hamster genomic DNA was used to create the uncloned, adapter-ligated genomic fragment libraries.
To create uncloned, adapter ligated genomic fragment libraries, genomic DNA was purified from hamster cells. Four separate aliquots were thoroughly digested with PvuII, StuI, DraI, or EcoRV. Following digestion, inactivation of the restriction enzymes, and dephosphorylation, each separate pool of DNA fragments was ligated to an adapter AP1 SEQ ID NO: 489 or AP2 SEQ ID NO: 490, see FIG. 5. The adapter was phosphorylated to provide the requisite phosphate group for a ligation reaction.
Also note that the 3-prime side of the short adapter contains an amine group to prevent the adapters from forming concatamers.
Two gene specific primers (GSP1 and GSP2) were designed for each region of known sequence (i.e., the exons of the INGAP gene). See FIG. 6 for fragment location and GSP1 and GSP2 location. The gene specific primers were designed as reverse PCR primers for all fragments except fragments 1_2 and 14_5. The gene specific primers for fragments 1_2 and 14_5 were designed as forward primers. Adapter primer 1 (AP1) and adapter primer 2 (AP2) (FIG. 5) were forward PCR primers for all fragments except fragments 1_2 and 14_5, which were reverse PCR primers. The outer gene specific primer (GSP1) was used with adapter primer 1 in a PCR reaction. To increase specificity, a second, nested PCR was set up using the inner gene specific primer (GSP2) and adapter primer 2. A small aliquot of the first reaction served as template for the second reaction. Gene specific PCR primers utilized for gene walking are listed in Table 2 and the strategy used to build the INGAP genomic sequence is shown in FIGS. 6 and 7. The arrowheads in FIG. 6 represent the adapter primers (AP1 and AP2), while the circles represent the gene specific primers (GSP1 and GSP2).
TABLE 2
NAME (LOCATION) SEQUENCE
INGEN 21_3 (1464, 1482) 5′-ACAAGCAATCTAGAGATGG-3′ (SEQ ID NO: 3)
INGEN 19_3 (1401, 1423) 5′-GTTCAGCTATGTTCATAGCAGGG-3′ (SEQ ID NO: 4)
INGEN 16_3 (1855, 1876) 5′-GTCTGTATGACTGTGTGGGAAG-3′ (SEQ ID NO: 5)
INGEN 15_3 (1929, 1948) 5′-GCACTTGAACTCAATGGCTC-3′ (SEQ ID NO: 6)
INGEN 14_3 (2147, 2168) 5′-GAACCACCTGACATGGGTGATG-3′ (SEQ ID NO: 7)
INGEN 13_3 (2177, 2200) 5′-GGGCATCGTATCATCTGGTTACAG-3′ (SEQ ID NO: 8)
INGEN 8_3 (2544, 2565) 5′-GGTTCAAAAAAGCTGCTTCAAC-3′ (SEQ ID NO: 9)
INGEN 7_3 (2666, 2689) 5′-GGAATAGCTGCAATTTATGCCCAT-3′ (SEQ ID NO: 10)
INGEN 4_3 (2833, 2858) 5′-CTTAGGAACATTCAGGCAGCCTCCTG-3′ (SEQ ID NO: 11)
INGEN 3_3 (2866, 2891) 5′-GTTGCCCTCTGCCACGTGTCAAGTTC-3′ (SEQ ID NO: 12)
INGEN 2_3 (3444, 3470) 5′-CATCCAAGACATCCTACAGAGGGTCAT-3′ (SEQ ID NO: 13)
INGEN 1_3 (3475, 3501) 5′-CCCAAGAAAGGAACATCAGGCAGGAAA-3′ (SEQ ID NO: 14)
INGEN 2_2 (3330, 3350) 5′-CCAAATGAGTGCTTCCCTGAA-3′ (SEQ ID NO: 15)
INGEN 1_2 (3241, 3266) 5′-GCAGCACTCTGAAACTCAGTAGAGTT-3′ (SEQ ID NO: 16)
INGEN 14_5 (5544, 5563) 5′-GCTGCTGACCGTGGTTATTG-3′ (SEQ ID NO: 17)
INGEN 13_5 (5463, 5485) 5′-ACACTACCCAACGGAAGTGGATG-3′ (SEQ ID NO: 18)
INGAP1_1L (3475, 3492) 5′-TTTCCTGCCTGATGTTCC-3′ (SEQ ID NO: 19)
INGAP1_1R (5957, 5976) 5′-TCATACTTGCTTCCTTGTCC-3′ (SEQ ID NO: 20)
INGAP2_1L (4470, 4488) 5′-CTTCACGTATAACCTGTCC-3′ (SEQ ID NO: 21)
INGAP2_1R (5905, 5923) 5′-ATTAGAACTGCCCTAGACC-3′ (SEQ ID NO: 22)
The PCR fragments were sequenced to determine the nucleotide sequence of the INGAP 5′-regulatory region, the introns, the intron/exon junctions, and the 3-prime polyadenylation regions. The nucleotide sequence of hamster INGAP genomic DNA is shown in SEQ ID NO: 2.
Example 2 Cloning Hamster INGAP 5′-Regulatory Region Fragment into a Reporter Construct To construct the INGAP 5′-regulatory region, individual PCR fragments were joined together at unique restriction sites located within two adjoining fragments. FIGS. 6 and 7 detail the strategy used to piece the INGAP 5′-regulatory region together. Fragments 8_3 and 2_3 were joined at a unique SphI site; 14_3 and 8_3 were joined at a unique BbsI site; 16_3 and 14_3 were joined at a unique PstI site. The nucleotide sequence of hamster INGAP 5′-regulatory region DNA is shown in SEQ ID NO: 1 and 23 in the sequence listing.
The hamster INGAP 5′-regulatory region or a fragment of the 5′-regulatory region was cloned into a reporter plasmid, pβGal-Basic (Clontech). The 5′-regulatory region or fragments were cloned utilizing the unique XmaI site from the gene walking adapter primer and a unique BgIII site located at the 3-prime side of the regulatory region. FIG. 8 details the fragments cloned into pβGal-Basic. The sizes of the fragments are indicated to the right of the fragments and are expressed as the number of nucleotides of the fragment.
Example 3 Assay System to Screen for Factors that Modulate the Expression of INGAP Promoter analysis of INGAP identified a number of potential promoter-proximal regulatory sites including the consensus transcription factor binding sites; cAMP response element (CRE), AP-1 and STAT. Promoter-fragment reporter-gene constructs were transiently transfected into 293T cells and co-transfection of secretory alkaline phosphatase was used to normalize for transfection efficiency.
Reporter constructs containing INGAP 5′-regulatory region fragments 2_3sP (SEQ ID NO: 37), 2_3dP (SEQ ID NO: 38), 2_3pP (SEQ ID NO: 36), 14_3P (SEQ ID NO: 34), 16_3P (SEQ ID NO: 31), or 19_3P (SEQ ID NO: 23) were transfected into human cells. The pβGal-Basic plasmid without the hamster INGAP DNA was also transfected into human cells as a control to measure the level of endogenous reporter activity. Two days following transfection, the cells were treated with PMA for 24 hours or were untreated. To determine the level of promoter activity, the amount of β-galactosidase gene product was determined using a luminescent assay for β-galactosidase. FIG. 9A shows that construct 14_3P activated the INGAP expression the most, followed by 2_3pP, and 16_3P.
Reporter construct containing INGAP 5′-regulatory region DNA nucleotides 2030 to 3120 was transfected into human cells. The pβGal-Basic plasmid without the hamster INGAP DNA was also transfected into human cells as a control to measure the level of endogenous reporter activity. Two days following transfection, the cells were treated with LIF for 24 hours or were untreated. To determine the level of promoter activity, the amount of β-galactosidase gene product was determined using a luminescent assay for β-galactosidase. FIG. 9B shows the results. LIF was determined to increase the activity of the 5′-regulatory region of mammalian INGAP. Forskolin (an activator of cAMP/CREB/CRE) did not modulate gene expression (data not shown).
It is important to note that when present in human cells, the hamster INGAP 5′-regulatory region is transactivated by the human transcription factors. Thus, linked to a reporter gene, the 5′-regulatory region of hamster INGAP creates a sensitive assay system to screen for factors that modulate the expression of INGAP.
Example 4 Determination of Approximate Location of PMA and LIF-Mediated Transcription Factor Binding in the 5′-Regulatory Region To map the approximate location of PMA-initiated or LIF-initiated transcription factor binding different fragments of the hamster INGAP 5′-regulatory region were cloned into pβGal-Basic. See FIG. 8. The fragments cloned into the reporter construct were 2_3sP (SEQ ID NO: 37), 2_3dP (SEQ ID NO: 38), 2_3pP (SEQ ID NO: 36), 14_3P (SEQ ID NO: 34), 16_3P (SEQ ID NO: 31), or 19_3P (SEQ ID NO: 23). The reporter constructs were transfected into human cells. Two days following transfection, the cells were treated with different concentrations of PMA or LIF for 24 hours. The concentrations of PMA used were 6 ng/ml, 17 ng/ml, 50 ng/ml, 100 ng/ml, or 300 ng/ml. The concentrations of LIF used were 1 ng/ml, 10 ng/ml, or 30 ng/ml. To determine the level of promoter activity, the amount of β-galactosidase gene product was determined using a luminescent assay for β-galactosidase. FIGS. 10 and 11 show the results for PMA and LIF treatment, respectively. Both PMA and LIF activated the cell reporter constructs. The exact location of the DNA contact sites can be narrowed further by cloning smaller fragments of the hamster INGAP 5′-regulatory region and by site directed mutations or deletions.
Example 5 RNA Analysis of INGAP Gene Upregulation To determine if INGAP RNA levels increase after stimulation with a cytokine that signals through STAT, rat amphocrine pancreatic cells, AR42J were treated with IL-6 (1000 U/ml) for 24 hours. Total RNA was extracted from the treated and untreated cells using techniques well known in the art, e.g., using TRIZOL® reagent.
Equal amounts of total RNA (10 μg) were loaded in 2.5% formaldehyde gel and electrophoresed for 4 hours at 70V with a constant circulation of the buffer using a circulating pump. The gel was photographed and washed with water twice at room temperature and soaked in 20×SSC. The gel was transferred to a nylon membrane (Amersham) in 20×SSC overnight following a standard procedure. The membrane was washed with 20×SSC to remove any agar that might have attached to the membrane and baked for 4 hours at 80° C.
One hundred nanograms of hamster INGAP cDNA was labeled using Random Prime Labeling kit (Roche-BMB) and alpha-P32 dCTP (ICN). Approximately 20 million counts were used for hybridization in 20 ml hybridization buffer following the standard procedure at 42° C. for overnight. The blot was washed as follows: 2-times at room temperature with 2×SSC for 10 minutes each; 2-times at 42° C. with 2×SSC for 10 minutes each; 2-times at 55° C. with 1×SSC for 10 minutes each. The membrane was exposed to the film (XOMAT-Kodak) and kept at −80° C. overnight before developing.
Treatment with IL-6 caused an increase in INGAP gene expression (FIG. 12). These data demonstrate that extracellular factors that elevate AP-1-binding transcription factors and STAT-binding transcription factors are involved in the regulation of INGAP gene expression. These studies suggest that it is feasible to enhance INGAP expression as a means of inducing islet neogenesis.
While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.
TABLE 3
SEQ
ID Further Position
NO: Family/matrix Information Opt. from-to anchor
SEQ V$LEFF/LEF1.01 TCF/LEF-1, 0.86 12-28 20
ID involved in the
NO: Wnt signal
41 transduction
pathway
SEQ V$MITF/MIT.01 MIT 0.81 22-40 31
ID (microphthalmia
NO: transcription
42 factor) and TFE3
SEQ V$OCT1/OCT1.05 octamer-binding 0.90 27-41 34
ID factor 1
NO:
43
SEQ V$TCFF/TCF11.01 TCF11/KCR- 1.00 32-38 35
ID F1/Nrf1
NO: homodimers
44
SEQ V$MYOF/MYOGNF1.01 Myogenin/ 0.71 25-53 39
ID nuclear factor 1
NO: or related factors
45
SEQ V$ZBPF/ZBP89.01 Zinc finger 0.93 36-48 42
ID transcription
NO: factor ZBP-89
46
SEQ V$SP1F/GC.01 GC box elements 0.88 38-52 45
ID
NO:
47
SEQ V$PERO/PPARA.01 PPAR/RXR 0.70 44-64 54
ID heterodimers
NO:
48
SEQ V$PAX5/PAX9.01 zebrafish PAX9 0.78 43-71 57
ID binding sites
NO:
49
SEQ V$TBPF/ATATA.01 Avian C-type LTR 0.81 68-84 76
ID TATA box
NO:
50
SEQ V$HMTB/MTBF.01 muscle-specific 0.90 76-84 80
ID Mt binding site
NO:
51
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 74-88 81
ID factor 1
NO:
52
NO: (en-1)
65
SEQ V$BARB/BARBIE.01 barbiturate- 0.88 230-244 237
ID inducible element
NO:
66
SEQ V$TBPF/TATA.01 cellular and viral 0.90 230-246 238
ID TATA box
NO: elements
67
SEQ V$BARB/BARBIE.01 barbiturate- 0.88 252-266 259
ID inducible element
NO:
68
SEQ V$MYT1/MYT1.01 MyT1 zinc finger 0.75 272-284 278
ID transcription
NO: factor involved in
69 primary
neurogenesis
SEQ V$SMAD/SMAD4.01 Smad4 0.94 304-312 308
ID transcription
NO: factor involved in
70 TGF-beta
signaling
SEQ V$HOXF/CRX.01 Cone-rod 0.94 312-328 320
ID homeobox-
NO: containing
71 transcription
factor/otx-like
homeobox gene
SEQ V$ECAT/NFY.01 nuclear factor Y 0.90 337-351 344
ID (Y-box binding
NO: factor)
72
SEQ V$HOXF/PTX1.01 Pituitary 0.79 337-353 345
ID Homeobox 1
NO: (Ptx1)
73
SEQ V$FKHD/FREAC2.01 Fork head 0.84 362-378 370
ID RElated
NO: ACtivator-2
74
SEQ V$MINI/MUSCLE_INI.02 Muscle Initiator 0.86 401-419 410
ID Sequence
NO:
75
SEQ V$MOKF/MOK2.01 Ribonucleoprotein 0.74 409-429 419
ID associated zinc
NO: finger protein
76 MOK-2 (mouse)
SEQ V$ZFIA/ZID.01 zinc finger with 0.85 414-426 420
ID interaction
NO: domain
77
SEQ V$CART/XVENT2.01 Xenopus 0.82 418-434 426
ID homeodomain
NO: factor Xvent-2;
78 early BMP
signaling
response
SEQ V$OCT1/OCT1.04 octamer-binding 0.80 421-435 428
ID factor 1
NO:
79
SEQ V$HOMS/S8.01 Binding site for 0.97 426-434 430
ID S8 type
NO: homeodomains
80
SEQ V$NKXH/NKX25.02 homeo domain 0.88 424-436 430
ID factor Nkx-
NO: 2.5/Csx, tinman
81 homolog low
affinity sites
SEQ V$CREB/CREBP1.01 cAMP-responsive 0.80 425-445 435
ID element binding
NO: protein 1
82
SEQ V$COMP/COMP1.01 COMP1, 0.76 434-454 444
ID cooperates with
NO: myogenic
83 proteins in
multicomponent
complex
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 444-460 452
ID vertebrate
NO: homeobox
84 protein
SEQ V$ETSF/GABP.01 GABP: GA 0.85 454-470 462
ID binding protein
NO:
85
SEQ V$LEFF/LEF1.01 TCF/LEF-1, 0.86 463-479 471
ID involved in the
NO: Wnt signal
86 transduction
pathway
SEQ V$STAT/STAT6.01 STAT6: signal 0.84 464-482 473
ID transducer and
NO: activator of
87 transcription 6
SEQ V$GATA/GATA1.03 GATA-binding 0.95 490-502 496
ID factor 1
NO:
88
SEQ V$SRFF/SRF.01 serum response 0.66 487-505 496
ID factor
NO:
89
SEQ V$EVI1/EVI1.04 Ecotropic viral 0.77 493-509 501
ID integration site 1
NO: encoded factor
90
SEQ V$AP4R/TH1E47.01 Thing1/E47 0.93 509-525 517
ID heterodimer, TH1
NO: bHLH member
91 specific
expression in a
variety of
embryonic
tissues
SEQ V$AP4R/TAL1BETAITF2.01 Tal-1beta/ITF-2 0.85 512-528 520
ID heterodimer
NO:
92
SEQ V$NEUR/NEUROD1.01 DNA binding site 0.83 514-526 520
ID for NEUROD1
NO: (BETA-2/E47
93 dimer)
SEQ V$MEF2/MEF2.05 MEF2 0.96 518-540 529
ID
NO:
94
SEQ V$EVI1/EVI1.04 Ecotropic viral 0.77 523-539 531
ID integration site 1
NO: encoded factor
95
SEQ V$MEF2/AMEF2.01 myocyte 0.80 521-543 532
ID enhancer factor
NO:
96
SEQ V$TBPF/MTATA.01 Muscle TATA box 0.84 524-540 532
ID
NO:
97
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 543-559 551
ID vertebrate
NO: homeobox
98 protein
SEQ V$PDX1/ISL1.01 Pancreatic and 0.82 543-563 553
ID intestinal lim-
NO: homeodomain
99 factor
SEQ V$OCT1/OCT1.05 octamer-binding 0.90 556-570 563
ID factor 1
NO:
100
SEQ V$CIZF/NMP4.01 NMP4 (nuclear 0.97 562-572 567
ID matrix protein 4)/
NO: CIZ (Cas-
101 interacting zinc
finger protein)
SEQ V$EVI1/EVI1.01 Ecotropic viral 0.72 569-585 577
ID integration site 1
NO: encoded factor
102
SEQ V$AP1F/AP1.01 AP1 binding site 0.95 582-602 592
ID
NO:
103
SEQ V$PIT1/PIT1.01 Pit1, GHF-1 0.86 589-599 594
ID pituitary specific
NO: pou domain
104 transcription
factor
SEQ V$AP1F/AP1.01 AP1 binding site 0.95 586-606 596
ID
NO:
105
SEQ V$VMYB/VMYB.01 v-Myb 0.90 593-603 598
ID
NO:
106
SEQ V$CIZF/NMP4.01 NMP4 (nuclear 0.97 595-605 600
ID matrix protein 4)/
NO: CIZ (Cas-
107 interacting zinc
finger protein)
SEQ V$GREF/PRE.01 Progesterone 0.84 604-622 613
ID receptor binding
NO: site
108
SEQ V$GKLF/GKLF.01 Gut-enriched 0.91 632-646 639
ID Krueppel-like
NO: factor
109
SEQ V$CIZF/NMP4.01 NMP4 (nuclear 0.97 637-647 642
ID matrix protein 4)/
NO: CIZ (Cas-
110 interacting zinc
finger protein)
SEQ V$NFAT/NFAT.01 Nuclear factor of 0.97 640-650 645
ID activated T-cells
NO:
111
SEQ V$MAZF/MAZ.01 Myc associated 0.90 649-661 655
ID zinc finger
NO: protein (MAZ)
112
SEQ V$EGRF/WT1.01 Wilms Tumor 0.88 658-672 665
ID Suppressor
NO:
113
SEQ V$ZBPF/ZBP89.01 Zinc finger 0.93 663-675 669
ID transcription
NO: factor ZBP-89
114
SEQ V$IRFF/IRF2.01 interferon 0.80 702-716 709
ID regulatory factor 2
NO:
115
SEQ V$BRNF/BRN2.01 POU factor Brn-2 0.91 746-762 754
ID (N-Oct 3)
NO:
116
SEQ V$ETSF/PU1.01 Pu.1 (Pu120) Ets- 0.86 746-762 754
ID like transcription
NO: factor identified
117 in lymphoid B-
cells
SEQ V$EVI1/EVI1.04 Ecotropic viral 0.77 750-766 758
ID integration site 1
NO: encoded factor
118
SEQ V$EVI1/EVI1.05 Ecotropic viral 0.80 755-771 763
ID integration site 1
NO: encoded factor
119
SEQ V$ZBPF/ZBP89.01 Zinc finger 0.93 764-776 770
ID transcription
NO: factor ZBP-89
120
SEQ V$FAST/FAST1.01 FAST-1 SMAD 0.81 769-783 776
ID interacting
NO: protein
121
SEQ V$TBPF/TATA.02 Mammalian C- 0.89 771-787 779
ID type LTR TATA
NO: box
122
SEQ V$PAX5/PAX9.01 zebrafish PAX9 0.78 781-809 795
ID binding sites
NO:
123
SEQ V$OCT1/OCT.01 Octamer binding 0.79 793-807 800
ID site (OCT1/OCT2
NO: consensus)
124
SEQ V$OCTP/OCT1P.01 octamer-binding 0.86 798-810 804
ID factor 1, POU-
NO: specific domain
125
SEQ V$SRFF/SRF.01 serum response 0.66 797-815 806
ID factor
NO:
126
SEQ V$EVI1/EVI1.05 Ecotropic viral 0.80 802-818 810
ID integration site 1
NO: encoded factor
127
SEQ V$CLOX/CDP.01 cut-like 0.75 803-819 811
ID homeodomain
NO: protein
128
SEQ V$EVI1/EVI1.02 Ecotropic viral 0.83 807-823 815
ID integration site 1
NO: encoded factor
129
SEQ V$ECAT/NFY.02 nuclear factor Y 0.91 810-824 817
ID (Y-box binding
NO: factor)
130
SEQ V$HAML/AML3.01 Runt-related 0.84 811-825 818
ID transcription
NO: factor 2/CBFA1
131 (core-binding
factor, runt
domain, alpha
subunit 1)
SEQ V$PCAT/CAAT.01 cellular and viral 0.90 813-823 818
ID CCAAT box
NO:
132
SEQ V$GATA/GATA.01 GATA binding site 0.95 818-830 824
ID (consensus)
NO:
133
SEQ V$HNF1/HNF1.02 Hepatic nuclear 0.76 818-834 826
ID factor 1
NO:
134
SEQ V$HOXT/MEIS1_HOXA9.01 Homeobox 0.79 823-835 829
ID protein MEIS1
NO: binding site
135
SEQ V$ECAT/NFY.01 nuclear factor Y 0.90 837-851 844
ID (Y-box binding
NO: factor)
136
SEQ V$FKHD/FREAC2.01 Fork head 0.84 844-860 852
ID RElated
NO: ACtivator-2
137
SEQ V$EVI1/EVI1.06 Ecotropic viral 0.83 846-862 854
ID integration site 1
NO: encoded factor
138
SEQ V$GATA/GATA1.01 GATA-binding 0.96 853-865 859
ID factor 1
NO:
139
SEQ V$PCAT/ACAAT.01 Avian C-type LTR 0.86 856-866 861
ID CCAAT box
NO:
140
SEQ V$XBBF/RFX1.01 X-box binding 0.89 909-927 918
ID protein RFX1
NO:
141
SEQ V$EBOX/MYCMAX.02 c-Myc/Max 0.92 912-928 920
ID heterodimer
NO:
142
SEQ V$MITF/MIT.01 MIT 0.81 911-929 920
ID (microphthalmia
NO: transcription
143 factor) and TFE3
SEQ V$ETSF/PU1.01 Pu.1 (Pu120) Ets- 0.86 927-943 935
ID like transcription
NO: factor identified
144 in lymphoid B-
cells
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 932-946 939
ID factor 1
NO:
145
SEQ V$TALE/TGIF.01 TG-interacting 1.00 936-942 939
ID factor belonging
NO: to TALE class of
146 homeodomain
factors
SEQ V$MITF/MIT.01 MIT 0.81 935-953 944
ID (microphthalmia
NO: transcription
147 factor) and TFE3
SEQ V$OCT1/OCT1.04 octamer-binding 0.80 941-955 948
ID factor 1
NO:
148
SEQ V$GATA/GATA.01 GATA binding site 0.95 962-974 968
ID (consensus)
NO:
149
SEQ V$SRFF/SRF.01 serum response 0.66 968-986 977
ID factor
NO:
150
SEQ V$CDXF/CDX2.01 Cdx-2 0.84 970-988 979
ID mammalian
NO: caudal related
151 intestinal transcr.
factor
SEQ V$FKHD/XFD2.01 Xenopus fork 0.89 972-988 980
ID head domain
NO: factor 2
152
SEQ V$MEF2/MEF2.01 myogenic 0.74 970-992 981
ID enhancer factor 2
NO:
153
SEQ V$TBPF/TATA.01 cellular and viral 0.90 973-989 981
ID TATA box
NO: elements
154
SEQ V$CART/CART1.01 Cart-1 (cartilage 0.84 978-994 986
ID homeoprotein 1)
NO:
155
SEQ V$CART/CART1.01 Cart-1 (cartilage 0.84 985-1001 993
ID homeoprotein 1)
NO:
156
SEQ V$SATB/SATB1.01 Special AT-rich 0.93 985-1001 993
ID sequence-binding
NO: protein 1,
157 predominantly
expressed in
thymocytes,
binds to matrix
attachment
regions (MARs)
SEQ V$BRNF/BRN3.01 POU transcription 0.78 987-1003 995
ID factor Brn-3
NO:
158
SEQ V$CLOX/CDP.01 cut-like 0.75 987-1003 995
ID homeodomain
NO: protein
159
SEQ V$HOMS/S8.01 Binding site for 0.97 992-1000 996
ID S8 type
NO: homeodomains
160
SEQ V$NKXH/DLX1.01 DLX-1, -2, and -5 0.91 990-1002 996
ID binding sites
NO:
161
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 989-1005 997
ID vertebrate
NO: homeobox
162 protein
SEQ V$PDX1/PDX1.01 Pdx1 (IDX1/IPF1) 0.74 988-1008 998
ID pancreatic and
NO: intestinal
163 homeodomain TF
SEQ V$FKHD/XFD3.01 Xenopus fork 0.82 998-1014 1006
ID head domain
NO: factor 3
164
SEQ V$HNF1/HNF1.01 hepatic nuclear 0.78 1000-1016 1008
ID factor 1
NO:
165
SEQ V$HNF1/HNF1.01 hepatic nuclear 0.78 1002-1018 1010
ID factor 1
NO:
166
SEQ V$PAX4/PAX4.01 Pax-4 paired 0.97 1005-1015 1010
ID domain protein,
NO: together with
167 PAX-6 involved in
pancreatic
development
SEQ V$HOMS/S8.01 Binding site for 0.97 1007-1015 1011
ID S8 type
NO: homeodomains
168
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 1003-1019 1011
ID vertebrate
NO: homeobox
169 protein
SEQ V$NKXH/DLX1.01 DLX-1, -2, and -5 0.91 1005-1017 1011
ID binding sites
NO:
170
SEQ V$RBIT/BRIGHT.01 Bright, B cell 0.92 1005-1017 1011
ID regulator of IgH
NO: transcription
171
SEQ V$TBPF/ATATA.01 Avian C-type LTR 0.81 1005-1021 1013
ID TATA box
NO:
172
SEQ V$CREB/CREBP1.01 cAMP-responsive 0.80 1004-1024 1014
ID element binding
NO: protein 1
173
SEQ V$RORA/RORA2.01 RAR-related 0.82 1007-1023 1015
ID orphan receptor
NO: alpha2
174
SEQ V$PCAT/CAAT.01 cellular and viral 0.90 1022-1032 1027
ID CCAAT box
NO:
175
SEQ V$NKXH/NKX25.02 homeo domain 0.88 1022-1034 1028
ID factor Nkx-
NO: 2.5/Csx, tinman
176 homolog low
affinity sites
SEQ V$CREB/HLF.01 hepatic leukemia 0.84 1022-1042 1032
ID factor
NO:
177
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 1056-1072 1064
ID vertebrate
NO: homeobox
178 protein
SEQ V$HOMS/S8.01 Binding site for 0.97 1061-1069 1065
ID S8 type
NO: homeodomains
179
SEQ V$NKXH/DLX1.01 DLX-1, -2, and -5 0.91 1059-1071 1065
ID binding sites
NO:
180
SEQ V$RBIT/BRIGHT.01 Bright, B cell 0.92 1059-1071 1065
ID regulator of IgH
NO: transcription
181
SEQ V$BRNF/BRN2.01 POU factor Brn-2 0.91 1058-1074 1066
ID (N-Oct 3)
NO:
182
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 1060-1074 1067
ID factor 1
NO:
183
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 1061-1077 1069
ID vertebrate
NO: homeobox
184 protein
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 1079-1093 1086
ID factor 1
NO:
185
SEQ V$FAST/FAST1.01 FAST-1 SMAD 0.81 1080-1094 1087
ID interacting
NO: protein
186
SEQ V$RREB/RREB1.01 Ras-responsive 0.79 1081-1095 1088
ID element binding
NO: protein 1
187
SEQ V$E2FF/E2F.02 E2F, involved in 0.84 1085-1099 1092
ID cell cycle
NO: regulation,
188 interacts with Rb
p107 protein
SEQ V$CREB/TAXCREB.01 Tax/CREB 0.81 1091-1111 1101
ID complex
NO:
189
SEQ V$AP1F/VMAF.01 v-Maf 0.82 1092-1112 1102
ID
NO:
190
SEQ V$MYT1/MYT1.01 MyT1 zinc finger 0.75 1123-1135 1129
ID transcription
NO: factor involved in
191 primary
neurogenesis
SEQ V$CLOX/CLOX.01 Clox 0.81 1136-1152 1144
ID
NO:
192
SEQ V$HNF4/HNF4.01 Hepatic nuclear 0.82 1156-1172 1164
ID factor 4
NO:
193
SEQ V$LEFF/LEF1.01 TCF/LEF-1, 0.86 1157-1173 1165
ID involved in the
NO: Wnt signal
194 transduction
pathway
SEQ V$PERO/PPARA.01 PPAR/RXR 0.70 1157-1177 1167
ID heterodimers
NO:
195
SEQ V$CLOX/CLOX.01 Clox 0.81 1173-1189 1181
ID
NO:
196
SEQ V$HNF6/HNF6.01 Liver enriched 0.82 1175-1189 1182
ID Cut -
NO: Homeodomain
197 transcription
factor HNF6
(ONECUT)
SEQ V$SRFF/SRF.02 serum response 0.83 1177-1195 1186
ID factor
NO:
198
SEQ V$CLOX/CDPCR3.01 cut-like 0.75 1180-1196 1188
ID homeodomain
NO: protein
199
SEQ V$PIT1/PIT1.01 Pit1, GHF-1 0.86 1186-1196 1191
ID pituitary specific
NO: pou domain
200 transcription
factor
SEQ V$HMTB/MTBF.01 muscle-specific 0.90 1196-1204 1200
ID Mt binding site
NO:
201
SEQ V$FKHD/HFH8.01 HNF-3/Fkh 0.92 1200-1216 1208
ID Homolog-8
NO:
202
SEQ V$E4FF/E4F.01 GLI-Krueppel- 0.82 1223-1235 1229
ID related
NO: transcription
203 factor, regulator
of adenovirus E4
promoter
SEQ V$CREB/HLF.01 hepatic leukemia 0.84 1221-1241 1231
ID factor
NO:
204
SEQ V$VBPF/VBP.01 PAR-type chicken 0.86 1226-1236 1231
ID vitellogenin
NO: promoter-binding
205 protein
SEQ V$OCT1/OCT.01 Octamer binding 0.79 1259-1273 1266
ID site (OCT1/OCT2
NO: consensus)
206
SEQ V$STAT/STAT6.01 STAT6: signal 0.84 1261-1279 1270
ID transducer and
NO: activator of
207 transcription 6
SEQ V$CDXF/CDX2.01 Cdx-2 0.84 1270-1288 1279
ID mammalian
NO: caudal related
208 intestinal transcr.
factor
SEQ V$SORY/SOX9.01 SOX (SRY-related 0.90 1280-1296 1288
ID HMG box)
NO:
209
SEQ V$FKHD/HFH2.01 HNF-3/Fkh 0.93 1285-1301 1293
ID Homolog 2
NO:
210
SEQ V$CDXF/CDX2.01 Cdx-2 0.84 1286-1304 1295
ID mammalian
NO: caudal related
211 intestinal transcr.
factor
SEQ V$OCTB/TST1.01 POU-factor Tst- 0.87 1288-1302 1295
ID 1/Oct-6
NO:
212
SEQ V$PDX1/ISL1.01 Pancreatic and 0.82 1298-1318 1308
ID intestinal lim-
NO: homeodomain
213 factor
SEQ V$SORY/SOX9.01 SOX (SRY-related 0.90 1308-1324 1316
ID HMG box)
NO:
214
SEQ V$CREB/HLF.01 hepatic leukemia 0.84 1310-1330 1320
ID factor
NO:
215
SEQ V$VBPF/VBP.01 PAR-type chicken 0.86 1315-1325 1320
ID vitellogenin
NO: promoter-binding
216 protein
SEQ V$CEBP/CEBPB.01 CCAAT/enhancer 0.94 1313-1331 1322
ID binding protein
NO: beta
217
SEQ V$PDX1/ISL1.01 Pancreatic and 0.82 1313-1333 1323
ID intestinal lim-
NO: homeodomain
218 factor
SEQ V$HAML/AML1.01 runt-factor AML-1 1.00 1323-1337 1330
ID
NO:
219
SEQ V$GREF/ARE.01 Androgene 0.80 1323-1341 1332
ID receptor binding
NO: site
220
SEQ V$TEAF/TEF1.01 TEF-1 related 0.84 1343-1355 1349
ID muscle factor
NO:
221
SEQ V$CMYB/CMYB.01 c-Myb, important 0.99 1352-1360 1356
ID in hematopoesis,
NO: cellular
222 equivalent to
avian
myoblastosis
virus oncogene v-
myb
SEQ V$AP4R/TH1E47.01 Thing1/E47 0.93 1378-1394 1386
ID heterodimer, TH1
NO: bHLH member
223 specific
expression in a
variety of
embryonic
tissues
SEQ V$CP2F/CP2.01 CP2 0.90 1384-1394 1389
ID
NO:
224
SEQ V$CHOP/CHOP.01 heterodimers of 0.90 1386-1398 1392
ID CHOP and
NO: C/EBPalpha
225
SEQ V$CEBP/CEBP.02 C/EBP binding 0.85 1385-1403 1394
ID site
NO:
226
SEQ V$MEF2/HMEF2.01 myocyte 0.76 1384-1406 1395
ID enhancer factor
NO:
227
SEQ V$OCT1/OCT1.03 octamer-binding 0.85 1388-1402 1395
ID factor 1
NO:
228
SEQ V$HMTB/MTBF.01 muscle-specific 0.90 1394-1402 1398
ID Mt binding site
NO:
229
SEQ V$CLOX/CDPCR3.01 cut-like 0.75 1422-1438 1430
ID homeodomain
NO: protein
230
SEQ V$OCT1/OCT1.05 octamer-binding 0.90 1423-1437 1430
ID factor 1
NO:
231
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 1423-1439 1431
ID vertebrate
NO: homeobox
232 protein
SEQ V$PDX1/PDX1.01 Pdx1 (IDX1/IPF1) 0.74 1423-1443 1433
ID pancreatic and
NO: intestinal
233 homeodomain TF
SEQ V$SORY/SOX5.01 Sox-5 0.87 1426-1442 1434
ID
NO:
234
SEQ V$OCT1/OCT1.05 octamer-binding 0.90 1444-1458 1451
ID factor 1
NO:
235
SEQ V$CREB/E4BP4.01 E4BP4, bZIP 0.80 1443-1463 1453
ID domain,
NO: transcriptional
236 repressor
SEQ V$VBPF/VBP.01 PAR-type chicken 0.86 1449-1459 1454
ID vitellogenin
NO: promoter-binding
237 protein
SEQ V$TBPF/MTATA.01 Muscle TATA box 0.84 1455-1471 1463
ID
NO:
238
SEQ V$PBXF/PBX1.01 homeo domain 0.78 1469-1481 1475
ID factor Pbx-1
NO:
239
SEQ V$COMP/COMP1.01 COMP1, 0.76 1467-1487 1477
ID cooperates with
NO: myogenic
240 proteins in
multicomponent
complex
SEQ V$SORY/S0X5.01 Sox-5 0.87 1478-1494 1486
ID
NO:
241
SEQ V$FKHD/FREAC2.01 Fork head 0.84 1485-1501 1493
ID RElated
NO: ACtivator-2
242
SEQ V$PDX1/ISL1.01 Pancreatic and 0.82 1495-1515 1505
ID intestinal lim-
NO: homeodomain
243 factor
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 1499-1515 1507
ID vertebrate
NO: homeobox
244 protein
SEQ V$PDX1/PDX1.01 Pdx1 (IDX1/IPF1) 0.74 1498-1518 1508
ID pancreatic and
NO: intestinal
245 homeodomain TF
SEQ V$CART/XVENT2.01 Xenopus 0.82 1502-1518 1510
ID homeodomain
NO: factor Xvent-2;
246 early BMP
signaling
response
SEQ V$CDXF/CDX2.01 Cdx-2 0.84 1507-1525 1516
ID mammalian
NO: caudal related
247 intestinal transcr.
factor
SEQ V$MEF2/MEF2.05 MEF2 0.96 1505-1527 1516
ID
NO:
248
SEQ V$HNF1/HNF1.01 hepatic nuclear 0.78 1510-1526 1518
ID factor 1
NO:
249
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 1511-1525 1518
ID factor 1
NO:
250
SEQ V$TBPF/TATA.02 Mammalian C- 0.89 1510-1526 1518
ID type LTR TATA
NO: box
251
SEQ V$NKXH/MSX.01 Homeodomain 0.97 1514-1526 1520
ID proteins MSX-1
NO: and MSX-2
252
SEQ V$RBIT/BRIGHT.01 Bright, B cell 0.92 1515-1527 1521
ID regulator of IgH
NO: transcription
253
SEQ V$MEF2/AMEF2.01 myocyte 0.80 1514-1536 1525
ID enhancer factor
NO:
254
SEQ V$EVI1/EVI1.02 Ecotropic viral 0.83 1526-1542 1534
ID integration site 1
NO: encoded factor
255
SEQ V$GATA/GATA1.02 GATA-binding 0.99 1528-1540 1534
ID factor 1
NO:
256
SEQ V$GATA/GATA3.02 GATA-binding 0.91 1537-1549 1543
ID factor 3
NO:
257
SEQ V$GATA/GATA3.02 GATA-binding 0.91 1559-1571 1565
ID factor 3
NO:
258
SEQ V$OCT1/OCT1.02 octamer-binding 0.82 1561-1575 1568
ID factor 1
NO:
259
SEQ V$CEBP/CEBPB.01 CCAAT/enhancer 0.94 1567-1585 1576
ID binding protein
NO: beta
260
SEQ V$PLZF/PLZF.01 Promyelocytic 0.86 1574-1588 1581
ID leukemia zink
NO: finger (TF with
261 nine Krueppel-
like zink fingers)
SEQ V$PAX3/PAX3.01 Pax-3 paired 0.76 1587-1599 1593
ID domain protein,
NO: expressed in
262 embryogenesis,
mutations
correlate to
Waardenburg
Syndrome
SEQ V$CREB/ATF.01 activating 0.90 1588-1608 1598
ID transcription
NO: factor
263
SEQ V$AP4R/TH1E47.01 Thing1/E47 0.93 1614-1630 1622
ID heterodimer, TH1
NO: bHLH member
264 specific
expression in a
variety of
embryonic
tissues
SEQ V$NKXH/MSX.01 Homeodomain 0.97 1619-1631 1625
ID proteins MSX-1
NO: and MSX-2
265
SEQ V$RBIT/BRIGHT.01 Bright, B cell 0.92 1620-1632 1626
ID regulator of IgH
NO: transcription
266
SEQ V$OCTB/TST1.01 POU-factor Tst- 0.87 1620-1634 1627
ID 1/Oct-6
NO:
267
SEQ V$NKXH/DLX3.01 Distal-less 3 0.91 1628-1640 1634
ID homeodomain
NO: transcription
268 factor
SEQ V$GREF/PRE.01 Progesterone 0.84 1628-1646 1637
ID receptor binding
NO: site
269
SEQ V$TBPF/TATA.01 cellular and viral 0.90 1636-1652 1644
ID TATA box
NO: elements
270
SEQ V$FKHD/XFD2.01 Xenopus fork 0.89 1637-1653 1645
ID head domain
NO: factor 2
271
SEQ V$TBPF/TATA.01 cellular and viral 0.90 1638-1654 1646
ID TATA box
NO: elements
272
SEQ V$CREB/E4BP4.01 E4BP4, bZIP 0.80 1638-1658 1648
ID domain,
NO: transcriptional
273 repressor
SEQ V$PDX1/ISL1.01 Pancreatic and 0.82 1644-1664 1654
ID intestinal lim-
NO: homeodomain
274 factor
SEQ V$COMP/COMP1.01 COMP1, 0.76 1648-1668 1658
ID cooperates with
NO: myogenic
275 proteins in
multicomponent
complex
SEQ V$TBPF/TATA.02 Mammalian C- 0.89 1658-1674 1666
ID type LTR TATA
NO: box
276
SEQ V$IRFF/ISRE.01 interferon- 0.81 1662-1676 1669
ID stimulated
NO: response element
277
SEQ V$XBBF/RFX1.01 X-box binding 0.89 1660-1678 1669
ID protein RFX1
NO:
278
SEQ V$MYT1/MYT1.02 MyT1 zinc finger 0.88 1667-1679 1673
ID transcription
NO: factor involved in
279 primary
neurogenesis
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 1683-1697 1690
ID factor 1
NO:
280
SEQ V$AP1F/TCF11MAFG.01 TCF11/MafG 0.81 1681-1701 1691
ID heterodimers,
NO: binding to
281 subclass of AP1
sites
SEQ V$NKXH/MSX2.01 Muscle segment 0.95 1687-1699 1693
ID homeo box 2,
NO: homologue of
282 Drosophila (HOX
8)
SEQ V$FAST/FAST1.01 FAST-1 SMAD 0.81 1687-1701 1694
ID interacting
NO: protein
283
SEQ V$PBXC/PBX1_MEIS1.03 Binding site for a 0.76 1686-1702 1694
ID Pbx1/Meis1
NO: heterodimer
284
SEQ V$CIZF/NMP4.01 NMP4 (nuclear 0.97 1699-1709 1704
ID matrix protein 4)/
NO: CIZ (Cas-
285 interacting zinc
finger protein)
SEQ V$STAT/STAT6.01 STAT6: signal 0.84 1702-1720 1711
ID transducer and
NO: activator of
286 transcription 6
SEQ V$AP4R/TAL1BETAE47.01 Tal-1beta/E47 0.87 1710-1726 1718
ID heterodimer
NO:
287
SEQ V$SORY/HMGIY.01 HMGI(Y) high- 0.92 1720-1736 1728
ID mobility-group
NO: protein I (Y),
288 architectural
transcription
factor organizing
the framework of
a nuclear protein-
DNA
transcriptional
complex
SEQ V$MYT1/MYT1.01 MyT1 zinc finger 0.75 1723-1735 1729
ID transcription
NO: factor involved in
289 primary
neurogenesis
SEQ V$SRFF/SRF.01 serum response 0.66 1728-1746 1737
ID factor
NO:
290
SEQ V$HOXF/HOXA9.01 Member of the 0.87 1731-1747 1739
ID vertebrate HOX -
NO: cluster of
291 homeobox factors
SEQ V$HOXT/MEIS1_HOXA9.01 Homeobox 0.79 1734-1746 1740
ID protein MEIS1
NO: binding site
292
SEQ V$PIT1/PIT1.01 Pit1, GHF-1 0.86 1737-1747 1742
ID pituitary specific
NO: pou domain
293 transcription
factor
SEQ V$AP1F/AP1.01 AP1 binding site 0.95 1734-1754 1744
ID
NO:
294
SEQ V$VBPF/VBP.01 PAR-type chicken 0.86 1746-1756 1751
ID vitellogenin
NO: promoter-binding
295 protein
SEQ V$FAST/FAST1.01 FAST-1 SMAD 0.81 1757-1771 1764
ID interacting
NO: protein
296
SEQ V$HOXF/EN1.01 Homeobox 0.77 1759-1775 1767
ID protein engrailed
NO: (en-1)
297
SEQ V$TBPF/MTATA.01 Muscle TATA box 0.84 1763-1779 1771
ID
NO:
298
SEQ V$ETSF/ETS2.01 c-Ets-2 binding 0.86 1774-1790 1782
ID site
NO:
299
SEQ V$MYT1/MYT1.02 MyT1 zinc finger 0.88 1780-1792 1786
ID transcription
NO: factor involved in
300 primary
neurogenesis
SEQ V$GFI1/GFI1.01 Growth factor 0.97 1782-1796 1789
ID independence 1
NO: zinc finger
301 protein acts as
transcriptional
repressor
SEQ V$TBPF/TATA.01 cellular and viral 0.90 1784-1800 1792
ID TATA box
NO: elements
302
SEQ V$BRNF/BRN2.01 POU factor Brn-2 0.91 1786-1802 1794
ID (N-Oct 3)
NO:
303
SEQ V$HOXT/MEIS1_HOXA9.01 Homeobox 0.79 1788-1800 1794
ID protein MEIS1
NO: binding site
304
SEQ V$MEF2/AMEF2.01 myocyte 0.80 1783-1805 1794
ID enhancer factor
NO:
305
SEQ V$OCTB/TST1.01 POU-factor Tst- 0.87 1787-1801 1794
ID 1/Oct-6
NO:
306
SEQ V$HOXF/HOXA9.01 Member of the 0.87 1787-1803 1795
ID vertebrate HOX-
NO: cluster of
307 homeobox factors
SEQ V$BRNF/BRN2.01 POU factor Brn-2 0.91 1788-1804 1796
ID (N-Oct 3)
NO:
308
SEQ V$PARF/DBP.01 Albumin D-box 0.84 1791-1805 1798
ID binding protein
NO:
309
SEQ V$OCT1/OCT1.02 octamer-binding 0.82 1795-1809 1802
ID factor 1
NO:
310
SEQ V$FKHD/FREAC2.01 Fork head 0.84 1816-1832 1824
ID RElated
NO: ACtivator-2
311
SEQ V$SORY/SOX5.01 Sox-5 0.87 1821-1837 1829
ID
NO:
312
SEQ V$AREB/AREB6.04 AREB6 (Atp1a1 0.98 1837-1849 1843
ID regulatory
NO: element binding
313 factor 6)
SEQ V$MYT1/MYT1.02 MyT1 zinc finger 0.88 1848-1860 1854
ID transcription
NO: factor involved in
314 primary
neurogenesis
SEQ V$RBPF/RBPJK.01 Mammalian 0.84 1851-1865 1858
ID transcriptional
NO: repressor RBP-
315 Jkappa/CBF1
SEQ V$OCT1/OCT1.02 octamer-binding 0.82 1875-1889 1882
ID factor 1
NO:
316
SEQ V$FKHD/FREAC4.01 Fork head 0.78 1875-1891 1883
ID RElated
NO: ACtivator-4
317
SEQ V$EBOX/MYCMAX.02 c-Myc/Max 0.92 1880-1896 1888
ID heterodimer
NO:
318
SEQ V$PAX6/PAX6.01 Pax-6 paired 0.75 1880-1898 1889
ID domain protein
NO:
319
SEQ V$IRFF/IRF3.01 Interferon 0.86 1891-1905 1898
ID regulatory factor
NO: 3 (IRF-3)
320
SEQ V$HNF1/HNF1.02 Hepatic nuclear 0.76 1895-1911 1903
ID factor 1
NO:
321
SEQ V$FKHD/FREAC2.01 Fork head 0.84 1898-1914 1906
ID RElated
NO: ACtivator-2
322
SEQ V$E4FF/E4F.01 GLI-Krueppel- 0.82 1902-1914 1908
ID related
NO: transcription
323 factor, regulator
of adenovirus E4
promoter
SEQ V$CREB/CREBP1.01 cAMP-responsive 0.80 1900-1920 1910
ID element binding
NO: protein 1
324
SEQ V$VBPF/VBP.01 PAR-type chicken 0.86 1905-1915 1910
ID vitellogenin
NO: promoter-binding
325 protein
SEQ V$MYT1/MYT1.01 MyT1 zinc finger 0.75 1912-1924 1918
ID transcription
NO: factor involved in
326 primary
neurogenesis
SEQ V$HNF1/HNF1.01 hepatic nuclear 0.78 1913-1929 1921
ID factor 1
NO:
327
SEQ V$PCAT/CAAT.01 cellular and viral 0.90 1928-1938 1933
ID CCAAT box
NO:
328
SEQ V$HNF6/HNF6.01 Liver enriched 0.82 1929-1943 1936
ID Cut-
NO: Homeodomain
329 transcription
factor HNF6
(ONECUT)
SEQ V$PXRF/PXRCAR.01 Halfsite of PXR 0.98 1935-1945 1940
ID (pregnane X
NO: receptor)/RXR
330 resp. CAR
(constitutive
androstane
receptor)/RXR
heterodimer
binding site
SEQ V$RARF/RTR.01 Retinoid 0.81 1934-1952 1943
ID receptor-related
NO: testis-associated
331 receptor
(GCNF/RTR)
SEQ V$HOXF/EN1.01 Homeobox 0.77 1936-1952 1944
ID protein engrailed
NO: (en-1)
332
SEQ V$NKXH/NKX25.01 homeo domain 1.00 1939-1951 1945
ID factor Nkx-
NO: 2.5/Csx, tinman
333 homolog, high
affinity sites
SEQ V$GATA/GATA3.02 GATA-binding 0.91 1953-1965 1959
ID factor 3
NO:
334
SEQ V$TBPF/TATA.01 cellular and viral 0.90 1968-1984 1976
ID TATA box
NO: elements
335
SEQ V$SRFF/SRF.01 serum response 0.66 1969-1987 1978
ID factor
NO:
336
SEQ V$CLOX/CDPCR3.01 cut-like 0.75 1972-1988 1980
ID homeodomain
NO: protein
337
SEQ V$PAX1/PAX1.01 Pax1 paired 0.61 2016-2034 2025
ID domain protein,
NO: expressed in the
338 developing
vertebral column
of mouse
embryos
SEQ V$TBPF/ATATA.01 Avian C-type LTR 0.81 2019-2035 2027
ID TATA box
NO:
339
SEQ V$GFI1/GfI1B.01 Growth factor 0.82 2021-2035 2028
ID independence 1
NO: zinc finger
340 protein Gfi-1B
SEQ V$NRSF/NRSF.01 neuron-restrictive 0.69 2025-2045 2035
ID silencer factor
NO:
341
SEQ V$NFAT/NFAT.01 Nuclear factor of 0.97 2033-2043 2038
ID activated T-cells
NO:
342
SEQ V$AREB/AREB6.04 AREB6 (Atp1a1 0.98 2034-2046 2040
ID regulatory
NO: element binding
343 factor 6)
SEQ V$HNF1/HNF1.01 hepatic nuclear 0.78 2036-2052 2044
ID factor 1
NO:
344
SEQ V$FKHD/XFD3.01 Xenopus fork 0.82 2038-2054 2046
ID head domain
NO: factor 3
345
SEQ V$PDX1/PDX1.01 Pdx1 (IDX1/IPF1) 0.74 2036-2056 2046
ID pancreatic and
NO: intestinal
346 homeodomain TF
SEQ V$OCT1/OCT1.01 octamer-binding 0.77 2050-2064 2057
ID factor 1
NO:
347
SEQ V$TBPF/TATA.01 cellular and viral 0.90 2053-2069 2061
ID TATA box
NO: elements
348
SEQ V$ETSF/GABP.01 GABP: GA 0.85 2080-2096 2088
ID binding protein
NO:
349
SEQ V$BEL1/BEL1.01 Bel-1 similar 0.78 2083-2105 2094
ID region (defined in
NO: Lentivirus LTRs)
350
SEQ V$VMYB/VMYB.01 v-Myb 0.90 2097-2107 2102
ID
NO:
351
SEQ V$GREF/ARE.01 Androgene 0.80 2106-2124 2115
ID receptor binding
NO: site
352
SEQ V$PDX1/PDX1.01 Pdx1 (IDX1/IPF1) 0.74 2137-2157 2147
ID pancreatic and
NO: intestinal
353 homeodomain TF
SEQ V$MYOD/MYOD.02 myoblast 0.98 2154-2168 2161
ID determining
NO: factor
354
SEQ V$GATA/GATA1.03 GATA-binding 0.95 2169-2181 2175
ID factor 1
NO:
355
SEQ V$AP4R/TAL1BETAE47.01 Tal-1beta/E47 0.87 2179-2195 2187
ID heterodimer
NO:
356
SEQ V$OAZF/ROAZ.01 Rat C2H2 Zn 0.73 2204-2220 2212
ID finger protein
NO: involved in
357 olfactory
neuronal
differentiation
SEQ V$GATA/GATA1.01 GATA-binding 0.96 2217-2229 2223
ID factor 1
NO:
358
SEQ V$MYOD/E47.02 TAL1/E47 dimers 0.93 2220-2234 2227
ID
NO:
359
SEQ V$LTUP/TAACC.01 Lentiviral TATA 0.71 2225-2247 2236
ID upstream
NO: element
360
SEQ V$RREB/RREB1.01 Ras-responsive 0.79 2239-2253 2246
ID element binding
NO: protein 1
361
SEQ V$OCT1/OCT1.05 octamer-binding 0.90 2251-2265 2258
ID factor 1
NO:
362
SEQ V$OCT1/OCT1.02 octamer-binding 0.82 2282-2296 2289
ID factor 1
NO:
363
SEQ V$COUP/COUP.01 COUP 0.81 2284-2298 2291
ID antagonizes HNF-
NO: 4 by binding site
364 competition or
synergizes by
direct protein -
protein
interaction with
HNF-4
SEQ V$MEF2/MEF2.01 myogenic 0.74 2290-2312 2301
ID enhancer factor 2
NO:
365
SEQ V$CDXF/CDX2.01 Cdx-2 0.84 2296-2314 2305
ID mammalian
NO: caudal related
366 intestinal transcr.
factor
SEQ V$MYT1/MYT1.01 MyT1 zinc finger 0.75 2301-2313 2307
ID transcription
NO: factor involved in
367 primary
neurogenesis
SEQ V$NFAT/NFAT.01 Nuclear factor of 0.97 2314-2324 2319
ID activated T-cells
NO:
368
SEQ V$CIZF/NMP4.01 NMP4 (nuclear 0.97 2317-2327 2322
ID matrix protein 4)/
NO: CIZ (Cas-
369 interacting zinc
finger protein)
SEQ V$GATA/GATA3.02 GATA-binding 0.91 2326-2338 2332
ID factor 3
NO:
370
SEQ V$HMTB/MTBF.01 muscle-specific 0.90 2351-2359 2355
ID Mt binding site
NO:
371
SEQ V$NOLF/OLF1.01 olfactory neuron- 0.82 2350-2372 2361
ID specific factor
NO:
372
SEQ V$PDX1/PDX1.01 Pdx1 (IDX1/IPF1) 0.74 2363-2383 2373
ID pancreatic and
NO: intestinal
373 homeodomain TF
SEQ V$GATA/GATA3.02 GATA-binding 0.91 2395-2407 2401
ID factor 3
NO:
374
SEQ V$NFAT/NFAT.01 Nuclear factor of 0.97 2406-2416 2411
ID activated T-cells
NO:
375
SEQ V$OCTP/OCT1P.01 octamer-binding 0.86 2433-2445 2439
ID factor 1, POU-
NO: specific domain
376
SEQ V$MITF/MIT.01 MIT 0.81 2438-2456 2447
ID (microphthalmia
NO: transcription
377 factor) and TFE3
SEQ V$PAX8/PAX8.01 PAX 2/5/8 0.88 2441-2453 2447
ID binding site
NO:
378
SEQ V$TBPF/ATATA.01 Avian C-type LTR 0.81 2451-2467 2459
ID TATA box
NO:
379
SEQ V$GATA/GATA3.02 GATA-binding 0.91 2462-2474 2468
ID factor 3
NO:
380
SEQ V$CLOX/CLOX.01 Clox 0.81 2462-2478 2470
ID
NO:
381
SEQ V$HNF6/HNF6.01 Liver enriched 0.82 2464-2478 2471
ID Cut -
NO: Homeodomain
382 transcription
factor HNF6
(ONECUT)
SEQ V$PIT1/PIT1.01 Pit1, GHF-1 0.86 2468-2478 2473
ID pituitary specific
NO: pou domain
383 transcription
factor
SEQ V$AP4R/TAL1BETAITF2.01 Tal-1beta/ITF-2 0.85 2469-2485 2477
ID heterodimer
NO:
384
SEQ V$CIZF/NMP4.01 NMP4 (nuclear 0.97 2477-2487 2482
ID matrix protein 4)/
NO: CIZ (Cas-
385 interacting zinc
finger protein)
SEQ V$NFAT/NFAT.01 Nuclear factor of 0.97 2480-2490 2485
ID activated T-cells
NO:
386
SEQ V$STAT/STAT.01 signal 0.87 2479-2497 2488
ID transducers and
NO: activators of
387 transcription
SEQ V$TBPF/TATA.02 Mammalian C- 0.89 2484-2500 2492
ID type LTR TATA
NO: box
388
SEQ V$FKHD/XFD3.01 Xenopus fork 0.82 2501-2517 2509
ID head domain
NO: factor 3
389
SEQ V$AP1F/AP1.01 AP1 binding site 0.95 2500-2520 2510
ID
NO:
390
SEQ V$AP1F/AP1.01 AP1 binding site 0.95 2504-2524 2514
ID
NO:
391
SEQ V$PCAT/CAAT.01 cellular and viral 0.90 2513-2523 2518
ID CCAAT box
NO:
392
SEQ V$CDXF/CDX2.01 Cdx-2 0.84 2524-2542 2533
ID mammalian
NO: caudal related
393 intestinal transcr.
factor
SEQ V$MYT1/MYT1.02 MyT1 zinc finger 0.88 2539-2551 2545
ID transcription
NO: factor involved in
394 primary
neurogenesis
SEQ V$ETSF/FLI.01 ETS family 0.81 2560-2576 2568
ID member FLI
NO:
395
SEQ V$MYT1/MYT1.01 MyT1 zinc finger 0.75 2569-2581 2575
ID transcription
NO: factor involved in
396 primary
neurogenesis
SEQ V$TBPF/ATATA.01 Avian C-type LTR 0.81 2576-2592 2584
ID TATA box
NO:
397
SEQ V$SATB/SATB1.01 Special AT-rich 0.93 2578-2594 2586
ID sequence-binding
NO: protein 1,
398 predominantly
expressed in
thymocytes,
binds to matrix
attachment
regions (MARs)
SEQ V$NKXH/NKX31.01 prostate-specific 0.84 2584-2596 2590
ID homeodomain
NO: protein NKX3.1
399
SEQ V$PARF/DBP.01 Albumin D-box 0.84 2589-2603 2596
ID binding protein
NO:
400
SEQ V$PAX5/PAX5.02 B-cell-specific 0.75 2591-2619 2605
ID activating protein
NO:
401
SEQ V$ECAT/NFY.03 nuclear factor Y 0.80 2604-2618 2611
ID (Y-box binding
NO: factor)
402
SEQ V$GFI1/GFI1.01 Growth factor 0.97 2608-2622 2615
ID independence 1
NO: zinc finger
403 protein acts as
transcriptional
repressor
SEQ V$HNF6/HNF6.01 Liver enriched 0.82 2608-2622 2615
ID Cut -
NO: Homeodomain
404 transcription
factor HNF6
(ONECUT)
SEQ V$MYT1/MYT1.01 MyT1 zinc finger 0.75 2610-2622 2616
ID transcription
NO: factor involved in
405 primary
neurogenesis
SEQ V$PAX8/PAX8.01 PAX 2/5/8 0.88 2610-2622 2616
ID binding site
NO:
406
SEQ V$TTFF/TTF1.01 Thyroid 0.92 2609-2623 2616
ID transcription
NO: factor-1 (TTF1)
407 binding site
SEQ V$MYT1/MYT1.02 MyT1 zinc finger 0.88 2612-2624 2618
ID transcription
NO: factor involved in
408 primary
neurogenesis
SEQ V$CDXF/CDX2.01 Cdx-2 0.84 2612-2630 2621
ID mammalian
NO: caudal related
409 intestinal transcr.
factor
SEQ V$SORY/HMGIY.01 HMGI(Y) high- 0.92 2649-2665 2657
ID mobility-group
NO: protein I (Y),
410 architectural
transcription
factor organizing
the framework of
a nuclear protein-
DNA
transcriptional
complex
SEQ V$HOXF/EN1.01 Homeobox 0.77 2657-2673 2665
ID protein engrailed
NO: (en-1)
411
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 2662-2676 2669
ID factor 1
NO:
412
SEQ V$BCL6/BCL6.01 POZ/zinc finger 0.76 2683-2699 2691
ID protein,
NO: transcriptional
413 repressor,
translocations
observed in
diffuse large cell
lymphoma
SEQ V$OCTP/OCT1P.01 octamer-binding 0.86 2715-2727 2721
ID factor 1, POU-
NO: specific domain
414
SEQ V$TEAF/TEF1.01 TEF-1 related 0.84 2722-2734 2728
ID muscle factor
NO:
415
SEQ V$GFI1/GFI1.01 Growth factor 0.97 2723-2737 2730
ID independence 1
NO: zinc finger
416 protein acts as
transcriptional
repressor
SEQ V$HOXT/MEIS1_HOXA9.01 Homeobox 0.79 2729-2741 2735
ID protein MEIS1
NO: binding site
417
SEQ V$HOXF/HOXA9.01 Member of the 0.87 2728-2744 2736
ID vertebrate HOX -
NO: cluster of
418 homeobox factors
SEQ V$PARF/DBP.01 Albumin D-box 0.84 2729-2743 2736
ID binding protein
NO:
419
SEQ V$VBPF/VBP.01 PAR-type chicken 0.86 2732-2742 2737
ID vitellogenin
NO: promoter-binding
420 protein
SEQ V$CREB/E4BP4.01 E4BP4, bZIP 0.80 2728-2748 2738
ID domain,
NO: transcriptional
421 repressor
SEQ V$OCT1/OCT1.01 octamer-binding 0.77 2733-2747 2740
ID factor 1
NO:
422
SEQ V$FKHD/XFD1.01 Xenopus fork 0.90 2733-2749 2741
ID head domain
NO: factor 1
423
SEQ V$SRFF/SRF.01 serum response 0.66 2736-2754 2745
ID factor
NO:
424
SEQ V$OCTP/OCT1P.01 octamer-binding 0.86 2746-2758 2752
ID factor 1, POU-
NO: specific domain
425
SEQ V$CLOX/CDPCR3.01 cut-like 0.75 2748-2764 2756
ID homeodomain
NO: protein
426
SEQ V$TBPF/TATA.01 cellular and viral 0.90 2749-2765 2757
ID TATA box
NO: elements
427
SEQ V$SRFF/SRF.01 serum response 0.66 2750-2768 2759
ID factor
NO:
428
SEQ V$TBPF/ATATA.01 Avian C-type LTR 0.81 2759-2775 2767
ID TATA box
NO:
429
SEQ V$TBPF/TATA.02 Mammalian C- 0.89 2762-2778 2770
ID type LTR TATA
NO: box
430
SEQ V$CABL/CABL.01 Multifunctional c- 0.97 2769-2779 2774
ID Abl src type
NO: tyrosine kinase
431
SEQ V$LEFF/LEF1.01 TCF/LEF-1, 0.86 2766-2782 2774
ID involved in the
NO: Wnt signal
432 transduction
pathway
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 2775-2789 2782
ID factor 1
NO:
433
SEQ V$MEF2/MMEF2.01 myocyte 0.90 2776-2798 2787
ID enhancer factor
NO:
434
SEQ V$OCT1/OCT1.06 octamer-binding 0.80 2780-2794 2787
ID factor 1
NO:
435
SEQ V$TBPF/TATA.01 cellular and viral 0.90 2779-2795 2787
ID TATA box
NO: elements
436
SEQ V$CART/CART1.01 Cart-1 (cartilage 0.84 2780-2796 2788
ID homeoprotein 1)
NO:
437
SEQ V$FKHD/XFD2.01 Xenopus fork- 0.89 2780-2796 2788
ID head domain
NO: factor 2
438
SEQ V$MEF2/MEF2.05 MEF2 0.96 2778-2800 2789
ID
NO:
439
SEQ V$BRNF/BRN3.01 POU transcription 0.78 2785-2801 2793
ID factor Brn-3
NO:
440
SEQ V$TBPF/TATA.01 cellular and viral 0.90 2786-2802 2794
ID TATA box
NO: elements
441
SEQ V$GFI1/GFI1.01 Growth factor 0.97 2791-2805 2798
ID independence 1
NO: zinc finger
442 protein acts as
transcriptional
repressor
SEQ V$HOXT/MEIS1_HOXA9.01 Homeobox 0.79 2797-2809 2803
ID protein MEIS1
NO: binding site
443
SEQ V$MEF2/MMEF2.01 myocyte 0.90 2792-2814 2803
ID enhancer factor
NO:
444
SEQ V$MEF2/MEF2.05 MEF2 0.96 2795-2817 2806
ID
NO:
445
SEQ V$MEF2/MMEF2.01 myocyte 0.90 2797-2819 2808
ID enhancer factor
NO:
446
SEQ V$HNF1/HNF1.01 hepatic nuclear 0.78 2802-2818 2810
ID factor 1
NO:
447
SEQ V$MEF2/MEF2.01 myogenic 0.74 2799-2821 2810
ID enhancer factor 2
NO:
448
SEQ V$HOXF/HOX1-3.01 Hox-1.3, 0.83 2814-2830 2822
ID vertebrate
NO: homeobox
449 protein
SEQ V$PARF/DBP.01 Albumin D-box 0.84 2816-2830 2823
ID binding protein
NO:
450
SEQ V$PDX1/ISL1.01 Pancreatic and 0.82 2814-2834 2824
ID intestinal lim-
NO: homeodomain
451 factor
SEQ V$GATA/GATA1.02 GATA-binding 0.99 2819-2831 2825
ID factor 1
NO:
452
SEQ V$HEAT/HSF1.01 heat shock factor 1 0.93 2845-2855 2850
ID
NO:
453
SEQ V$MYT1/MYT1.02 MyT1 zinc finger 0.88 2853-2865 2859
ID transcription
NO: factor involved in
454 primary
neurogenesis
SEQ V$BCL6/BCL6.02 POZ/zinc finger 0.77 2857-2873 2865
ID protein,
NO: transcriptional
455 repressor,
translocations
observed in
diffuse large cell
lymphoma
SEQ V$TTFF/TTF1.01 Thyroid 0.92 2863-2877 2870
ID transcription
NO: factor-1 (TTF1)
456 binding site
SEQ V$EBOX/USF.02 upstream 0.94 2868-2884 2876
ID stimulating factor
NO:
457
SEQ V$HOXF/PTX1.01 Pituitary 0.79 2892-2908 2900
ID Homeobox 1
NO: (Ptx1)
458
SEQ V$MYOD/LMO2COM.01 complex of Lmo2 0.98 2901-2915 2908
ID bound to Tal-1,
NO: E2A proteins, and
459 GATA-1, half-site 1
SEQ V$REBV/EBVR.01 Epstein-Barr 0.81 2904-2924 2914
ID virus
NO: transcription
460 factor R
SEQ V$ETSF/PU1.01 Pu.1 (Pu120) Ets- 0.86 2932-2948 2940
ID like transcription
NO: factor identified
461 in lymphoid B-
cells
SEQ V$MITF/MIT.01 MIT 0.81 2943-2961 2952
ID (microphthalmia
NO: transcription
462 factor) and TFE3
SEQ V$HAML/AML1.01 runt-factor AML-1 1.00 2950-2964 2957
ID
NO:
463
SEQ V$NFKB/CREL.01 c-Rel 0.91 2954-2968 2961
ID
NO:
464
SEQ V$IKRS/IK3.01 Ikaros 3, 0.84 2958-2970 2964
ID potential
NO: regulator of
465 lymphocyte
differentiation
SEQ V$RBPF/RBPJK.01 Mammalian 0.84 2957-2971 2964
ID transcriptional
NO: repressor RBP-
466 Jkappa/CBF1
SEQ V$E2FF/E2F.01 E2F, involved in 0.74 2966-2980 2973
ID cell cycle
NO: regulation,
467 interacts with Rb
p107 protein
SEQ V$E4FF/E4F.01 GLI-Krueppel- 0.82 2968-2980 2974
ID related
NO: transcription
468 factor, regulator
of adenovirus E4
promoter
SEQ V$CREB/ATF6.02 Activating 0.85 2966-2986 2976
ID transcription
NO: factor 6, member
469 of b-zip family,
induced by ER
stress
SEQ V$EBOX/ARNT.01 AhR nuclear 0.89 2968-2984 2976
ID translocator
NO: homodimers
470
SEQ V$E4FF/E4F.01 GLI-Krueppel- 0.82 2971-2983 2977
ID related
NO: transcription
471 factor, regulator
of adenovirus E4
promoter
SEQ V$EBOR/XBP1.01 X-box-binding 0.86 2970-2984 2977
ID protein 1
NO:
472
SEQ V$E2FF/E2F.01 E2F, involved in 0.74 2971-2985 2978
ID cell cycle
NO: regulation,
473 interacts with Rb
p107 protein
SEQ V$STAT/STAT.01 signal 0.87 2989-3007 2998
ID transducers and
NO: activators of
474 transcription
SEQ V$BCL6/BCL6.02 POZ/zinc finger 0.77 2991-3007 2999
ID protein,
NO: transcriptional
475 repressor,
translocations
observed in
diffuse large cell
lymphoma
SEQ V$XSEC/STAF.01 Se-Cys tRNA 0.77 3003-3025 3014
ID gene
NO: transcription
476 activating factor
SEQ V$NF1F/NF1.01 Nuclear factor 1 0.94 3007-3025 3016
ID
NO:
477
SEQ V$OCT1/OCT1.02 octamer-binding 0.82 3014-3028 3021
ID factor 1
NO:
478
SEQ V$RCAT/CLTR_CAAT.01 Mammalian C- 0.75 3019-3043 3031
ID type LTR CCAAT
NO: box
479
SEQ V$SF1F/SF1.01 SF1 steroidogenic 0.95 3033-3045 3039
ID factor 1
NO:
480
SEQ V$OCT1/OCT1.01 octamer-binding 0.77 3038-3052 3045
ID factor 1
NO:
481
SEQ V$PARF/DBP.01 Albumin D-box 0.84 3042-3056 3049
ID binding protein
NO:
482
SEQ V$ETSF/ETS1.01 c-Ets-1 binding 0.92 3057-3073 3065
ID site
NO:
483
SEQ V$LEFF/LEF1.01 TCF/LEF-1, 0.86 3062-3078 3070
ID involved in the
NO: Wnt signal
484 transduction
pathway
SEQ V$MAZF/MAZ.01 Myc associated 0.90 3072-3084 3078
ID zinc finger
NO: protein (MAZ)
485
SEQ V$SP1F/GC.01 GC box elements 0.88 3071-3085 3078
ID
NO:
486
SEQ V$TBPF/TATA.01 cellular and viral 0.90 3091-3107 3099
ID TATA box
NO:
487 elements
SEQ V$SEF1/SEF1.01 SEF1 binding site 0.69 3099-3117 3108
ID
NO:
488
SEQ
ID Core Matrix
NO: Str. sim. sim. Sequence
SEQ (+) 1.000 0.900 ggaccatCAAAgtctgt
ID
NO:
41
SEQ (+) 1.000 0.823 agtctgtCATGtcatttgg
ID
NO:
42
SEQ (+) 0.833 0.904 gTCATgtcatttggg
ID
NO:
43
SEQ (+) 1.000 1.000 GTCAttt
ID
NO:
44
SEQ (+) 1.000 0.735 ctgtcatgtcatTTGGgggagggcctatg
ID
NO:
45
SEQ (−) 1.000 0.982 gccctCCCCcaaa
ID
NO:
46
SEQ (+) 0.876 0.898 tgggGGAGggcctat
ID
NO:
47
SEQ (−) 0.884 0.708 acagaggagggcATAGgccct
ID
NO:
48
SEQ (−) 0.800 0.811 cagataCACAgaggagggcataggccctc
ID
NO:
49
SEQ (−) 1.000 0.987 tgctattTAAGcccaga
ID
NO:
50
SEQ (−) 1.000 0.932 tgctATTTa
ID
NO:
51
SEQ (−) 0.750 0.865 ggtatgctATTTaag
ID
NO:
52
NO:
65
SEQ (−) 1.000 0.894 ttatAAAGctgagga
ID
NO:
66
SEQ (−) 1.000 0.910 agttaTAAAgctgagga
ID
NO:
67
SEQ (−) 1.000 0.902 agtgAAAGcagagag
ID
NO:
68
SEQ (−) 0.750 0.756 craCAGTtgacct
ID
NO:
69
SEQ (+) 1.000 0.940 GTCTtgact
ID
NO:
70
SEQ (−) 1.000 0.960 gagggATTAgaaaagga
ID
NO:
71
SEQ (−) 1.000 0.906 ggaatCCAAtygtag
ID
NO:
72
SEQ (+) 0.789 0.802 ctacraTTGGattccat
ID
NO:
73
SEQ (−) 1.000 0.897 tacagcTAAAcactgag
ID
NO:
74
SEQ (−) 0.840 0.865 gagcctTCATccagtagct
ID
NO:
75
SEQ (−) 1.000 0.746 tgtcatcttagagCCTTcatc
ID
NO:
76
SEQ (+) 1.000 0.861 agGCTCtaagatg
ID
NO:
77
SEQ (+) 0.750 0.837 tcTAAGatgacaattaa
ID
NO:
78
SEQ (+) 0.807 0.840 aaGATGacaattaag
ID
NO:
79
SEQ (+) 1.000 0.994 gacaATTAa
ID
NO:
80
SEQ (−) 1.000 1.000 cctTAATtgtcat
ID
NO:
81
SEQ (−) 0.766 0.808 cgacgattACCTtaattgtca
ID
NO:
82
SEQ (−) 0.750 0.768 aatgaggATCGacgattacct
ID
NO:
83
SEQ (+) 1.000 0.886 cgatcctcATTAtagtg
ID
NO:
84
SEQ (+) 1.000 0.868 tatagtGGAAgggcttc
ID
NO:
85
SEQ (+) 1.000 0.904 agggcttCAAAggcagt
ID
NO:
86
SEQ (−) 0.758 0.867 gagacTGCCtttgaagccc
ID
NO:
87
SEQ (−) 1.000 0.971 ttcaGATAggcag
ID
NO:
88
SEQ (−) 0.757 0.672 atgttcaGATAggcagtag
ID
NO:
89
SEQ (−) 0.800 0.824 gGAAAtgttcagatagg
ID
NO:
90
SEQ (+) 1.000 0.951 cctaatgCCAGatgtct
ID
NO:
91
SEQ (+) 1.000 0.852 aatgcCAGAtgtctctt
ID
NO:
92
SEQ (−) 1.000 0.851 gagaCATCtggca
ID
NO:
93
SEQ (−) 1.000 0.984 aggataggttTAAAgagacatct
ID
NO:
94
SEQ (−) 1.000 0.774 gGATAggtttaaagaga
ID
NO:
95
SEQ (+) 1.000 0.813 tgtctcttTAAAcctatcctggc
ID
NO:
96
SEQ (+) 1.000 0.877 ctcttTAAAcctatcct
ID
NO:
97
SEQ (+) 1.000 0.845 ctcccttcATTAaggta
ID
NO:
98
SEQ (−) 1.000 0.834 gagatacctTAATgaagggag
ID
NO:
99
SEQ (+) 0.944 0.926 gGTATctcatttttt
ID
NO:
100
SEQ (−) 1.000 0.972 gcAAAAaatga
ID
NO:
101
SEQ (−) 0.764 0.720 ggaaCAGAggagagcaa
ID
NO:
102
SEQ (−) 0.881 0.964 aaaactgaATCAgtggnggaa
ID
NO:
103
SEQ (+) 1.000 0.886 actgATTCagt
ID
NO:
104
SEQ (+) 0.850 0.956 nccactgaTTCAgtttttctg
ID
NO:
105
SEQ (−) 0.876 0.910 aaaAACTgaat
ID
NO:
106
SEQ (−) 1.000 0.975 agAAAAactga
ID
NO:
107
SEQ (+) 1.000 0.875 ctgatccctctTGTTctcc
ID
NO:
108
SEQ (−) 1.000 0.971 gaaaaagagaAGGGa
ID
NO:
109
SEQ (−) 1.000 0.987 ggAAAAagaga
ID
NO:
110
SEQ (−) 1.000 0.982 ggagGAAAaag
ID
NO:
111
SEQ (−) 1.000 0.910 ggtgGAGGgaagg
ID
NO:
112
SEQ (−) 1.000 0.932 gggggTGGGagggtg
ID
NO:
113
SEQ (+) 1.000 0.972 tcccaCCCCcatg
ID
NO:
114
SEQ (−) 1.000 0.815 aggaagggGAAAggg
ID
NO:
115
SEQ (−) 1.000 0.911 aaaataggAAATaagga
ID
NO:
116
SEQ (−) 1.000 0.883 aaaataGGAAataagga
ID
NO:
117
SEQ (−) 0.760 0.792 aGAGAaaataggaaata
ID
NO:
118
SEQ (−) 0.763 0.817 cccccagagaaAATAgg
ID
NO:
119
SEQ (−) 1.000 0.934 ccacaCCCCcaga
ID
NO:
120
SEQ (+) 0.983 0.894 gggtgtgGATTttat
ID
NO:
121
SEQ (−) 1.000 0.942 caccaTAAAatccacac
ID
NO:
122
SEQ (−) 0.866 0.813 aacataTGCAcagaagggcttccaccata
ID
NO:
123
SEQ (−) 1.000 0.790 catATGCacagaagg
ID
NO:
124
SEQ (−) 1.000 0.910 caacatATGCaca
ID
NO:
125
SEQ (+) 0.757 0.666 ctgtgcaTATGttgtctta
ID
NO:
126
SEQ (−) 0.750 0.828 caataagacaaCATAtg
ID
NO:
127
SEQ (−) 1.000 0.776 ccAATAagacaacatat
ID
NO:
128
SEQ (−) 1.000 0.836 tcaaccaatAAGAcaac
ID
NO:
129
SEQ (−) 1.000 0.960 atcaaCCAAtaagac
ID
NO:
130
SEQ (+) 1.000 0.844 tcttatTGGTtgata
ID
NO:
131
SEQ (−) 1.000 0.943 tcaaCCAAtaa
ID
NO:
132
SEQ (+) 1.000 0.956 ggttGATAaataa
ID
NO:
133
SEQ (+) 0.757 0.791 gGTTGataaataaagca
ID
NO:
134
SEQ (−) 0.750 0.797 gTGCTttatttat
ID
NO:
135
SEQ (+) 1.000 0.912 gttgtCCAAtaggga
ID
NO:
136
SEQ (+) 0.750 0.843 aataggGAAAcaagata
ID
NO:
137
SEQ (+) 1.000 0.960 tagggaaacaAGATagg
ID
NO:
138
SEQ (+) 1.000 0.970 acaaGATAggtgg
ID
NO:
139
SEQ (−) 0.750 0.867 cccaCCTAtct
ID
NO:
140
SEQ (−) 1.000 0.929 ggatcacatgGCAAccctc
ID
NO:
141
SEQ (−) 0.895 0.936 ggatCACAtggcaacc
ID
NO:
142
SEQ (+) 1.000 0.863 gggttgcCATGtgatccta
ID
NO:
143
SEQ (+) 1.000 0.950 ctaggaGGAAttgacac
ID
NO:
144
SEQ (−) 1.000 0.800 catgtgtcAATTcct
ID
NO:
145
SEQ (−) 1.000 1.000 tGTCAat
ID
NO:
146
SEQ (−) 1.000 0.835 ccattctCATGtgtcaatt
ID
NO:
147
SEQ (+) 0.846 0.800 caCATGagaatgggg
ID
NO:
148
SEQ (+) 1.000 0.998 gaaaGATAagtcc
ID
NO:
149
SEQ (−) 1.000 0.672 atattttTATAaggactta
ID
NO:
150
SEQ (−) 1.000 0.867 atatattTTTAtaaggact
ID
NO:
151
SEQ (+) 1.000 0.894 tccttaTAAAaatatat
ID
NO:
152
SEQ (+) 1.000 0.740 agtccttaTAAAaatatatatta
ID
NO:
153
SEQ (+) 1.000 0.963 ccttaTAAAaatatata
ID
NO:
154
SEQ (−) 1.000 0.870 acTAATatatattttta
ID
NO:
155
SEQ (−) 1.000 0.855 caTAATtactaatatat
ID
NO:
156
SEQ (−) 1.000 0.943 cataattacTAATatat
ID
NO:
157
SEQ (−) 1.000 0.816 cccATAAttactaatat
ID
NO:
158
SEQ (−) 0.757 0.765 ccCATAattactaatat
ID
NO:
159
SEQ (+) 1.000 0.989 agtaATTAt
ID
NO:
160
SEQ (−) 1.000 0.976 ccatAATTactaa
ID
NO:
161
SEQ (−) 1.000 0.886 aacccataATTActaat
ID
NO:
162
SEQ (−) 1.000 0.775 attaacccaTAATtactaata
ID
NO:
163
SEQ (+) 0.826 0.844 tatgggttAATAattaa
ID
NO:
164
SEQ (−) 0.755 0.857 aCTTAattattaaccca
ID
NO:
165
SEQ (+) 1.000 0.966 gGTTAataattaagtca
ID
NO:
166
SEQ (+) 1.000 0.972 taatAATTaag
ID
NO:
167
SEQ (−) 1.000 0.995 cttaATTAt
ID
NO:
168
SEQ (−) 1.000 0.873 ctgacttaATTAttaac
ID
NO:
169
SEQ (+) 1.000 0.988 taatAATaagtc
ID
NO:
170
SEQ (+) 1.000 0.931 taataATTAagtc
ID
NO:
171
SEQ (+) 1.000 0.881 taataatTAAGtcagag
ID
NO:
172
SEQ (−) 0.766 0.819 tagctctgACTTaattattaa
ID
NO:
173
SEQ (+) 0.750 0.874 ataattaAGTCagagct
ID
NO:
174
SEQ (+) 0.856 0.928 ctagCCATtaa
ID
NO:
175
SEQ (−) 1.000 0.903 tctTAATggctag
ID
NO:
176
SEQ (−) 0.770 0.842 ctagtGTTTcttaatggctag
ID
NO:
177
SEQ (+) 1.000 0.891 gcttcataATTAatata
ID
NO:
178
SEQ (−) 1.000 0.995 attaATTAt
ID
NO:
179
SEQ (+) 1.000 0.988 tcatAATTaatat
ID
NO:
180
SEQ (+) 1.000 0.952 tcataATTAatat
ID
NO:
181
SEQ (+) 1.000 0.945 ttcataatTAATatagt
ID
NO:
182
SEQ (−) 1.000 0.885 actatattAATTatg
ID
NO:
183
SEQ (−) 1.000 0.854 gatactatATTAattat
ID
NO:
184
SEQ (+) 0.750 0.875 tgtatgttCATTtgg
ID
NO:
185
SEQ (+) 0.850 0.887 gtatgttCATTtggg
ID
NO:
186
SEQ (−) 1.000 0.816 cCCCAaatgaacata
ID
NO:
187
SEQ (−) 1.000 0.849 tcagcccCAAAtgaa
ID
NO:
188
SEQ (+) 1.000 0.828 tggggcTGACacagttctggg
ID
NO:
189
SEQ (+) 1.000 0.833 ggggcTGACacagttctggga
ID
NO:
190
SEQ (+) 0.750 0.791 aggAAGAytactt
ID
NO:
191
SEQ (−) 0.804 0.820 cctacaATCCatgtacc
ID
NO:
192
SEQ (−) 1.000 0.864 atagagCAAAggactac
ID
NO:
193
SEQ (−) 1.000 0.907 catagagCAAAggacta
ID
NO:
194
SEQ (−) 1.000 0.700 tagacatagagcAAAGgacta
ID
NO:
195
SEQ (+) 0.804 0.831 gtctaaATCCatatatg
ID
NO:
196
SEQ (+) 0.833 0.929 ctaaaTCCAtatatg
ID
NO:
197
SEQ (+) 1.000 0.851 aaatCCATatatgaatgag
ID
NO:
198
SEQ (−) 1.000 0.761 actcattcatatATGGa
ID
NO:
199
SEQ (−) 1.000 0.919 actcATTCata
ID
NO:
200
SEQ (−) 0.807 0.901 tggtATGTa
ID
NO:
201
SEQ (−) 1.000 0.922 gaaagayAAACatggta
ID
NO:
202
SEQ (−) 0.789 0.898 gtgAGGTaacccc
ID
NO:
203
SEQ (+) 1.000 0.854 atgggGTTAcctcactcagga
ID
NO:
204
SEQ (+) 1.000 0.903 gTTACctcact
ID
NO:
205
SEQ (−) 0.758 0.870 cgcAGGCaaatgaat
ID
NO:
206
SEQ (+) 0.758 0.850 tcattTGCCtgcgaatttt
ID
NO:
207
SEQ (+) 1.000 0.869 tgcgaatTTTAagattcca
ID
NO:
208
SEQ (−) 1.000 0.990 taaaaCAATggaatctt
ID
NO:
209
SEQ (−) 1.000 0.931 aggaataaAACAatgga
ID
NO:
210
SEQ (+) 1.000 0.865 ccattgtTTTAttcctctg
ID
NO:
211
SEQ (−) 0.894 0.876 gaggAATAaaacaat
ID
NO:
212
SEQ (+) 1.000 0.824 tcctctgagTAATactccatt
ID
NO:
213
SEQ (−) 1.000 0.925 ttacaCAATggagtatt
ID
NO:
214
SEQ (−) 0.901 0.920 ggtacATTAcacaatggagta
ID
NO:
215
SEQ (−) 1.000 0.871 aTTACacaatg
ID
NO:
216
SEQ (+) 0.929 0.955 tccattgtGTAAtgtacca
ID
NO:
217
SEQ (+) 1.000 0.859 tccattgtgTAATgtaccaca
ID
NO:
218
SEQ (−) 1.000 1.000 aaaatgTGGTacatt
ID
NO:
219
SEQ (+) 0.750 0.819 aatgtaccacaTTTTctcc
ID
NO:
220
SEQ (+) 1.000 0.896 taCATTcttcagt
ID
NO:
221
SEQ (+) 1.000 0.990 caGTTGagg
ID
NO:
222
SEQ (−) 1.000 0.932 gcaatagCCAGaacctg
ID
NO:
223
SEQ (−) 1.000 0.945 gcaatagCCAG
ID
NO:
224
SEQ (−) 1.000 0.951 attTGCAatagcc
ID
NO:
225
SEQ (+) 1.000 0.853 tggctattGCAAataaccc
ID
NO:
226
SEQ (+) 1.000 0.809 ctggctattgcAAATaaccctgc
ID
NO:
227
SEQ (+) 1.000 0.889 ctattgcAAATaacc
ID
NO:
228
SEQ (−) 1.000 0.900 ggttATTTg
ID
NO:
229
SEQ (+) 0.975 0.761 acatatgtcattATTGt
ID
NO:
230
SEQ (+) 0.944 0.938 cATATgtcattattg
ID
NO:
231
SEQ (+) 1.000 0.836 catatgtcATTAttgta
ID
NO:
232
SEQ (−) 1.000 0.889 ttcatacaaTAATgacatatg
ID
NO:
233
SEQ (−) 1.000 0.870 tcataCAATaatgacat
ID
NO:
234
SEQ (−) 0.944 0.914 aATATgtaaaacaga
ID
NO:
235
SEQ (−) 1.000 0.856 tttaaaatatGTAAaacagat
ID
NO:
236
SEQ (+) 1.000 0.886 tTTACatattt
ID
NO:
237
SEQ (+) 1.000 0.841 tatttTAAAccatctct
ID
NO:
238
SEQ (−) 1.000 0.783 caagCAATctaga
ID
NO:
239
SEQ (+) 1.000 0.765 tctctagATTGcttgtaatat
ID
NO:
240
SEQ (−) 1.000 0.997 tttaaCAATattacaag
ID
NO:
241
SEQ (+) 1.000 0.885 tattgtTAAAcatagag
ID
NO:
242
SEQ (+) 1.000 0.839 catagagagTAATaatgctat
ID
NO:
243
SEQ (−) 1.000 0.872 atagcattATTActctc
ID
NO:
244
SEQ (−) 0.826 0.843 tttatagcaTTATtactctct
ID
NO:
245
SEQ (+) 1.000 0.829 agTAATaatgctataaa
ID
NO:
246
SEQ (−) 1.000 0.906 tttaattTTTAtagcatta
ID
NO:
247
SEQ (+) 1.000 0.983 aataatgctaTAAAaattaaaaa
ID
NO:
248
SEQ (−) 0.755 0.805 tTTTAatttttatagca
ID
NO:
249
SEQ (+) 1.000 0.832 gctataaaAATTaaa
ID
NO:
250
SEQ (+) 1.000 0.991 tgctaTAAAaattaaaa
ID
NO:
251
SEQ (−) 1.000 0.989 tttTAATttttat
ID
NO:
252
SEQ (+) 1.000 0.944 taaaaATTAaaaa
ID
NO:
253
SEQ (+) 1.000 0.807 ataaaaatTAAAaataatgataa
ID
NO:
254
SEQ (+) 1.000 0.872 aataatgatAAGAaaga
ID
NO:
255
SEQ (+) 1.000 0.993 taatGATAagaaa
ID
NO:
256
SEQ (+) 1.000 0.931 gaaAGATcctata
ID
NO:
257
SEQ (+) 1.000 0.915 tacAGATgaaaat
ID
NO:
258
SEQ (+) 0.763 0.867 cagATGAaaatttag
ID
NO:
259
SEQ (+) 0.985 0.964 aaaatttaGAAAtacttta
ID
NO:
260
SEQ (−) 0.958 0.866 agcTAAAgtatttct
ID
NO:
261
SEQ (−) 1.000 0.763 TCGTcagtggtag
ID
NO:
262
SEQ (+) 1.000 0.923 taccacTGACgaaatttgtat
ID
NO:
263
SEQ (−) 1.000 0.959 tttaattCCAGacattc
ID
NO:
264
SEQ (−) 1.000 0.977 cttTAATtccaga
ID
NO:
265
SEQ (+) 1.000 0.923 ctggaATTAaaga
ID
NO:
266
SEQ (+) 1.000 0.898 ctggAATTaaagaaa
ID
NO:
267
SEQ (−) 1.000 0.915 cagTAATttcttt
ID
NO:
268
SEQ (+) 1.000 0.922 aaagaaattacTGTTcttt
ID
NO:
269
SEQ (−) 1.000 0.934 ttataTAAAgaacagta
ID
NO:
270
SEQ (−) 1.000 0.890 attataTAAAgaacagt
ID
NO:
271
SEQ (−) 0.891 0.923 tattaTATAaagaacag
ID
NO:
272
SEQ (−) 0.769 0.856 ctattattatATAAagaacag
ID
NO:
273
SEQ (+) 1.000 0.836 tttatataaTAATagactgta
ID
NO:
274
SEQ (+) 0.791 0.760 tataataATAGactgtaaaat
ID
NO:
275
SEQ (+) 1.000 0.912 gactgTAAAatggcaac
ID
NO:
276
SEQ (+) 0.750 0.817 gtaaaatgGCAActt
ID
NO:
277
SEQ (+) 1.000 0.907 ctgtaaaatgGCAActttt
ID
NO:
278
SEQ (−) 1.000 0.882 taaAAGTtgccat
ID
NO:
279
SEQ (+) 1.000 0.878 tatttgctAATTcac
ID
NO:
280
SEQ (−) 0.777 0.865 tcctgTGAAttagcaaatatt
ID
NO:
281
SEQ (+) 1.000 0.969 tgCTAAttcacag
ID
NO:
282
SEQ (−) 0.850 0.866 tcctgtgAATTagca
ID
NO:
283
SEQ (+) 0.750 0.788 ttgctaatTCACaggat
ID
NO:
284
SEQ (−) 1.000 0.973 agAAAAaatcc
ID
NO:
285
SEQ (−) 1.000 0.908 agatgTTCCaaagaaaaaa
ID
NO:
286
SEQ (−) 1.000 0.919 ttgttCAGAtgttccaa
ID
NO:
287
SEQ (+) 1.000 0.953 tgaacaAATTtccctta
ID
NO:
288
SEQ (+) 0.750 0.757 acaAATTtccctt
ID
NO:
289
SEQ (+) 1.000 0.771 tttccctTATAtgaatcac
ID
NO:
290
SEQ (−) 1.000 0.908 agtGATTcatataaggg
ID
NO:
291
SEQ (−) 1.000 0.797 gTGATtcatataa
ID
NO:
292
SEQ (−) 1.000 0.912 agtgATTCata
ID
NO:
293
SEQ (+) 0.881 0.958 ttatatgaATCActtacattt
ID
NO:
294
SEQ (+) 1.000 0.860 cTTACattttt
ID
NO:
295
SEQ (+) 0.850 0.829 gcctgttCATTtaaa
ID
NO:
296
SEQ (−) 1.000 0.832 gtttTTTAaatgaacag
ID
NO:
297
SEQ (+) 1.000 0.853 tcattTAAAaaactgca
ID
NO:
298
SEQ (+) 1.000 0.866 actgcAGGAaagttgtg
ID
NO:
299
SEQ (+) 1.000 0.891 ggaAAGTtgtgat
ID
NO:
300
SEQ (−) 1.000 1.000 ataAATCacaacttt
ID
NO:
301
SEQ (−) 1.000 0.931 cattaTAAAtcacaact
ID
NO:
302
SEQ (−) 1.000 0.933 tgcattatAAATcacaa
ID
NO:
303
SEQ (+) 1.000 0.924 gTGATttataatg
ID
NO:
304
SEQ (−) 0.866 0.827 agttgcatTATAaatcacaactt
ID
NO:
305
SEQ (+) 0.894 0.898 tgtgATTTataatgc
ID
NO:
306
SEQ (+) 1.000 0.971 tgtGATTtataatgcaa
ID
NO:
307
SEQ (+) 1.000 0.916 gtgatttaTAATgcaac
ID
NO:
308
SEQ (+) 0.884 0.891 atttaTAATgcaact
ID
NO:
309
SEQ (+) 1.000 0.861 ataATGCaactgcac
ID
NO:
310
SEQ (+) 1.000 0.910 cagtctTAAAcaatgct
ID
NO:
311
SEQ (+) 1.000 0.992 ttaaaCAATgctaacca
ID
NO:
312
SEQ (+) 1.000 0.981 actgtGTTTcagc
ID
NO:
313
SEQ (−) 1.000 0.889 gggAAGTttatgc
ID
NO:
314
SEQ (−) 1.000 0.878 tgtgTGGGaagttta
ID
NO:
315
SEQ (+) 0.763 0.826 actATGAaaacacat
ID
NO:
316
SEQ (+) 1.000 0.786 actatgaaAACAcatgc
ID
NO:
317
SEQ (+) 0.895 0.920 gaaaaCACAtgcttaaa
ID
NO:
318
SEQ (−) 0.773 0.791 cctttAAGCatgtgttttc
ID
NO:
319
SEQ (+) 1.000 0.874 cttaaaggCAAAtct
ID
NO:
320
SEQ (−) 0.858 0.782 aGGTAaagatttgcctt
ID
NO:
321
SEQ (−) 1.000 0.853 ctgaggTAAAgatttgc
ID
NO:
322
SEQ (−) 0.789 0.830 ctgAGGTaaagat
ID
NO:
323
SEQ (+) 0.766 0.820 aaatctttACCTcagttaact
ID
NO:
324
SEQ (+) 1.000 0.862 tTTACctcagt
ID
NO:
325
SEQ (−) 0.750 0.775 gaaTAGTtaactg
ID
NO:
326
SEQ (+) 1.000 0.811 aGTTAactattccatag
ID
NO:
327
SEQ (+) 0.856 0.925 agagCCATtga
ID
NO:
328
SEQ (−) 1.000 0.873 tgaacTCAAtggctc
ID
NO:
329
SEQ (−) 1.000 0.980 ctTGAActcaa
ID
NO:
330
SEQ (+) 1.000 0.854 attgagtTCAAgtgcattt
ID
NO:
331
SEQ (+) 0.782 0.813 tgagTTCAagtgcattt
ID
NO:
332
SEQ (+) 1.000 1.000 gttcAAGTgcatt
ID
NO:
333
SEQ (+) 1.000 0.928 agaAGATataatg
ID
NO:
334
SEQ (−) 0.891 0.912 atataTATAtggccata
ID
NO:
335
SEQ (+) 1.000 0.777 atggccaTATAtatatata
ID
NO:
336
SEQ (−) 1.000 0.806 atatatatatatATGGc
ID
NO:
337
SEQ (−) 0.750 0.675 CTGTgctgatatatatata
ID
NO:
338
SEQ (+) 0.750 0.827 atatataTCAGcacagt
ID
NO:
339
SEQ (+) 1.000 0.904 ataTATCagcacagt
ID
NO:
340
SEQ (+) 1.000 0.704 atcAGCAcagtggaaacagtt
ID
NO:
341
SEQ (+) 1.000 0.970 agtgGAAAcag
ID
NO:
342
SEQ (−) 1.000 0.991 taactGTTTccac
ID
NO:
343
SEQ (−) 1.000 0.798 tGTTAttaactgtttcc
ID
NO:
344
SEQ (+) 0.826 0.824 aaacagttAATAacatt
ID
NO:
345
SEQ (+) 1.000 0.749 ggaaacagtTAATaacatttt
ID
NO:
346
SEQ (−) 1.000 0.863 taTATGctaaaatgt
ID
NO:
347
SEQ (−) 0.891 0.908 tagtaTATAtgctaaaa
ID
NO:
348
SEQ (+) 1.000 0.897 gaggctGGAAgggggct
ID
NO:
349
SEQ (+) 1.000 0.787 gctggaagggggcTCAGcagtta
ID
NO:
350
SEQ (−) 0.876 0.901 attAACTgctg
ID
NO:
351
SEQ (+) 0.750 0.840 atagcacatacTATTcttc
ID
NO:
352
SEQ (+) 0.782 0.747 gtttggtttTCATcacccatg
ID
NO:
353
SEQ (−) 1.000 0.988 gaacCACCtgacatg
ID
NO:
354
SEQ (−) 1.000 0.958 tacaGATAgaaat
ID
NO:
355
SEQ (+) 1.000 0.924 gtaacCAGAtgatacga
ID
NO:
356
SEQ (−) 0.750 0.762 agGTACccaaggggact
ID
NO:
357
SEQ (−) 1.000 0.960 aggtGATAgaggt
ID
NO:
358
SEQ (−) 1.000 0.939 atagCAGGtgataga
ID
NO:
359
SEQ (+) 0.759 0.710 cacctgctattctCACCcaaaga
ID
NO:
360
SEQ (+) 1.000 0.805 aCCCAaagacacaca
ID
NO:
361
SEQ (−) 0.944 0.904 tGTATgtgagtgtgt
ID
NO:
362
SEQ (+) 1.000 0.854 tgcATGCacatagtt
ID
NO:
363
SEQ (−) 0.977 0.855 tGAACtatgtgcatg
ID
NO:
364
SEQ (+) 0.750 0.767 catagttcAAAAaataaaatttt
ID
NO:
365
SEQ (−) 1.000 0.896 ttaaaatTTTAttttttga
ID
NO:
366
SEQ (−) 0.750 0.798 taaAATTttattt
ID
NO:
367
SEQ (+) 1.000 0.991 aaagGAAAaaa
ID
NO:
368
SEQ (+) 1.000 0.977 ggAAAAaaagc
ID
NO:
369
SEQ (−) 1.000 0.946 aaaAGATttgagc
ID
NO:
370
SEQ (−) 1.000 0.901 aggaATTTt
ID
NO:
371
SEQ (+) 0.806 0.820 taaaatTCCTatgagtgtgtgat
ID
NO:
372
SEQ (−) 0.782 0.753 tactgacttTGATcacacact
ID
NO:
373
SEQ (−) 1.000 0.942 cacAGATtatacc
ID
NO:
374
SEQ (+) 1.000 0.971 tgtgGAAAaca
ID
NO:
375
SEQ (+) 0.980 0.879 ctcagtATTCaca
ID
NO:
376
SEQ (−) 1.000 0.827 ctactttCATGtgtgaata
ID
NO:
377
SEQ (−) 0.850 0.952 cttTCATgtgtga
ID
NO:
378
SEQ (+) 1.000 0.838 aagtagcTAAGaataaa
ID
NO:
379
SEQ (−) 1.000 0.960 aatAGATtttatt
ID
NO:
380
SEQ (+) 0.806 0.819 aataaaATCTattcatc
ID
NO:
381
SEQ (+) 0.785 0.846 taaaaTCTAttcatc
ID
NO:
382
SEQ (+) 1.000 0.890 atctATTCatc
ID
NO:
383
SEQ (−) 1.000 0.881 aaaaaCAGAtgaataga
ID
NO:
384
SEQ (−) 1.000 0.981 ggAAAAacaga
ID
NO:
385
SEQ (−) 1.000 0.976 taagGAAAaac
ID
NO:
386
SEQ (−) 1.000 0.872 aggattttaaGGAAaaaca
ID
NO:
387
SEQ (+) 1.000 0.897 ttcctTAAAatcctggc
ID
NO:
388
SEQ (−) 1.000 0.880 actgagtcAACActgta
ID
NO:
389
SEQ (−) 1.000 0.984 accactgaGTCAacactgtag
ID
NO:
390
SEQ (+) 0.964 0.984 agtgttgaCTCAgtggttgct
ID
NO:
391
SEQ (−) 0.826 0.904 gcaaCCACtga
ID
NO:
392
SEQ (+) 1.000 0.883 tttaaatTTTAtgctcaaa
ID
NO:
393
SEQ (+) 1.000 0.891 caaAAGTtgaagc
ID
NO:
394
SEQ (+) 1.000 0.829 tgaaCCGGtaattctac
ID
NO:
395
SEQ (−) 1.000 0.757 acaAAGTagaatt
ID
NO:
396
SEQ (−) 0.750 0.816 aagtattTAATacaaag
ID
NO:
397
SEQ (−) 1.000 0.939 acaagtattTAATacaa
ID
NO:
398
SEQ (−) 1.000 0.865 taacAAGTattta
ID
NO:
399
SEQ (+) 1.000 0.882 acttgTTATgcatcg
ID
NO:
400
SEQ (−) 1.000 0.758 aacttgatttgttgAGCGatgcataacaa
ID
NO:
401
SEQ (+) 0.750 0.809 ctcaaCAAAtcaagt
ID
NO:
402
SEQ (+) 1.000 0.976 acaAATCaagtttta
ID
NO:
403
SEQ (+) 1.000 0.830 acaaaTCAAgtttta
ID
NO:
404
SEQ (−) 0.750 0.756 taaAACTtgattt
ID
NO:
405
SEQ (+) 1.000 0.907 aaaTCAAgtttta
ID
NO:
406
SEQ (+) 1.000 0.936 caaatCAAGttttaa
ID
NO:
407
SEQ (+) 1.000 0.887 atcAAGTtttaac
ID
NO:
408
SEQ (+) 1.000 0.883 atcaagtTTTAacacacca
ID
NO:
409
SEQ (−) 1.000 0.925 ttaaaaAATTtaagata
ID
NO:
410
SEQ (+) 1.000 0.780 atttTTTAaatgggcat
ID
NO:
411
SEQ (−) 0.750 0.818 tttatgccCATTtaa
ID
NO:
412
SEQ (+) 1.000 0.796 ctaTTCCtacagaagtc
ID
NO:
413
SEQ (+) 1.000 0.860 ctgaaaATGCatt
ID
NO:
414
SEQ (+) 1.000 0.898 tgCATTcctgatt
ID
NO:
415
SEQ (−) 1.000 0.981 ataAATCaggaatgc
ID
NO:
416
SEQ (+) 1.000 0.929 cTGATttatgtaa
ID
NO:
417
SEQ (+) 1.000 0.964 cctGATTtatgtaaata
ID
NO:
418
SEQ (+) 1.000 0.861 ctgatTTATgtaaat
ID
NO:
419
SEQ (−) 1.000 0.929 tTTACataaat
ID
NO:
420
SEQ (+) 1.000 0.943 cctgatttatGTAAatatatg
ID
NO:
421
SEQ (+) 1.000 0.895 ttTATGtaaatatat
ID
NO:
422
SEQ (+) 1.000 0.940 tttatgTAAAtatatgt
ID
NO:
423
SEQ (+) 1.000 0.691 atgtaaaTATAtgtatata
ID
NO:
424
SEQ (+) 0.849 0.883 atgtatATACata
ID
NO:
425
SEQ (+) 0.888 0.755 gtatatacatatATAGc
ID
NO:
426
SEQ (−) 0.891 0.903 ggctaTATAtgtatata
ID
NO:
427
SEQ (+) 1.000 0.709 atatacaTATAtagcctta
ID
NO:
428
SEQ (−) 1.000 0.816 ttgttttTAAGgctata
ID
NO:
429
SEQ (+) 1.000 0.899 agcctTAAAaacaaaga
ID
NO:
430
SEQ (+) 1.000 0.973 aaAACAaagat
ID
NO:
431
SEQ (+) 1.000 0.863 ttaaaaaCAAAgattgt
ID
NO:
432
SEQ (+) 1.000 0.811 aagattgtAATTttt
ID
NO:
433
SEQ (−) 1.000 0.900 acaatttaTAAAaattacaatct
ID
NO:
434
SEQ (−) 1.000 0.844 tttataaaAATTaca
ID
NO:
435
SEQ (−) 1.000 0.956 atttaTAAAaattacaa
ID
NO:
436
SEQ (+) 1.000 0.875 tgTAATttttataaatt
ID
NO:
437
SEQ (−) 1.000 0.903 aatttaTAAAaattaca
ID
NO:
438
SEQ (−) 1.000 0.973 tcacaatttaTAAAaattacaat
ID
NO:
439
SEQ (−) 0.750 0.798 atcACAAtttataaaaa
ID
NO:
440
SEQ (+) 1.000 0.927 ttttaTAAAttgtgatt
ID
NO:
441
SEQ (−) 1.000 0.997 aaaAATCacaattta
ID
NO:
442
SEQ (+) 1.000 0.806 gTGATttttaaaa
ID
NO:
443
SEQ (−) 1.000 0.923 tattttttTAAAaatcacaattt
ID
NO:
444
SEQ (+) 1.000 0.990 ttgtgattttTAAAaaaataaac
ID
NO:
445
SEQ (+) 1.000 0.905 gtgattttTAAAaaaataaacct
ID
NO:
446
SEQ (−) 0.755 0.796 gGTTTatttttttaaaa
ID
NO:
447
SEQ (+) 0.750 0.775 gatttttaAAAAaataaacctgc
ID
NO:
448
SEQ (+) 1.000 0.848 aaacctgcATTAtcttc
ID
NO:
449
SEQ (−) 0.884 0.851 gaagaTAATgcaggt
ID
NO:
450
SEQ (−) 1.000 0.853 tgctgaagaTAATgcaggttt
ID
NO:
451
SEQ (−) 1.000 0.993 tgaaGATAatgca
ID
NO:
452
SEQ (+) 0.867 0.951 TGAAtgttcct
ID
NO:
453
SEQ (+) 1.000 0.893 cctAAGTtttgta
ID
NO:
454
SEQ (+) 1.000 0.772 agttttgTAGAacttga
ID
NO:
455
SEQ (−) 1.000 0.927 cgtgtCAAGttctac
ID
NO:
456
SEQ (−) 1.000 0.997 tctgccaCGTGtcaagt
ID
NO:
457
SEQ (+) 1.000 0.795 aggattTTAGtctacac
ID
NO:
458
SEQ (−) 1.000 0.981 gatgCAGGtgtagac
ID
NO:
459
SEQ (−) 1.000 0.832 ctgtcctcagatgcaGGTGta
ID
NO:
460
SEQ (+) 1.000 0.873 ctaacaGGAAaggagac
ID
NO:
461
SEQ (+) 1.000 0.829 ggagacaCATGtgtggtag
ID
NO:
462
SEQ (+) 1.000 1.000 catgtgTGGTagttc
ID
NO:
463
SEQ (+) 1.000 0.919 tgtggtagTTCCcag
ID
NO:
464
SEQ (−) 1.000 0.841 aactgGGAActac
ID
NO:
465
SEQ (−) 1.000 0.842 aaacTGGGaactacc
ID
NO:
466
SEQ (−) 0.750 0.784 ttcacgtCAAAactg
ID
NO:
467
SEQ (−) 1.000 0.830 ttcACGTcaaaac
ID
NO:
468
SEQ (+) 1.000 0.985 cagttttGACGtgaaaagtcc
ID
NO:
469
SEQ (+) 1.000 0.891 gttttgaCGTGaaaagt
ID
NO:
470
SEQ (+) 1.000 0.909 ttgACGTgaaaag
ID
NO:
471
SEQ (+) 1.000 0.890 tttgACGTgaaaagt
ID
NO:
472
SEQ (+) 1.000 0.837 ttgacgtGAAAagtc
ID
NO:
473
SEQ (+) 1.000 0.937 cattcttactGGAAacctc
ID
NO:
474
SEQ (+) 0.800 0.805 ttcttacTGGAaacctc
ID
NO:
475
SEQ (+) 0.782 0.791 acctCCCTgaatccatgccaagc
ID
NO:
476
SEQ (−) 1.000 0.964 gctTGGCatggattcaggg
ID
NO:
477
SEQ (+) 1.000 0.820 tccATGCcaagcact
ID
NO:
478
SEQ (+) 1.000 0.787 gCCAAgcactacccatcaccttgac
ID
NO:
479
SEQ (−) 1.000 0.954 cagtCAAGgtgat
ID
NO:
480
SEQ (−) 1.000 0.800 ctTATGccagtcaag
ID
NO:
481
SEQ (−) 1.000 0.862 agtgcTTATgccagt
ID
NO:
482
SEQ (−) 1.000 0.920 atcaaAGGAaatgagtg
ID
NO:
483
SEQ (−) 1.000 0.969 ggggcatCAAAggaaat
ID
NO:
484
SEQ (−) 1.000 0.912 gaggGAGGggcat
ID
NO:
485
SEQ (−) 0.876 0.920 tgagGGAGgggcatc
ID
NO:
486
SEQ (+) 1.000 0.973 tattaTAAAagcacagt
ID
NO:
487
SEQ (−) 1.000 0.700 gaaagagacgaCTGTgctt
ID
NO:
488
