Abstract: Disclosed are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.

Abstract: Work described herein reveals 3D regulatory landscapes of hESCs representative of early human development. This work also demonstrates that cohesin-associated CTCF loops, and the cohesin-associate enhancer-promoter loops within them, dominate the organization of TADs. The CTCF-CTCF loops form a chromosomal scaffold of insulated neighborhoods that are largely preserved in vertebrates, and enhancer-promoter interactions occur within these neighborhoods. Genes are regulated in the context of conserved insulated neighborhood structures. Loss of neighborhood structures occurs frequently in cancer cells, and proto-oncogenes can be activated by genetic alterations that disrupt specific 3D chromosome structures.

Abstract: Disclosed are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.

Abstract: Provided herein are improved compositions and methods for the directed control of gene expression.

Abstract: Provided herein are methods for identifying master transcription factors (TFs) in a cell type of interest and for transdifferentiation of a somatic cell, e.g., a fibroblast to the cell type of interest. Also provided herein are induced retinal pigment epithelium (iRPE) cell, master TFs therefor, methods for making iRPE cell, and methods and compositions for treating an ocular disease such as age-related macular degeneration.

Abstract: Disclosed herein are methods for identifying the core regulatory circuitry or cell identity program of a cell or tissue, and related methods of diagnoses, screening, and treatment involving the core regulatory circuitry and/or cell identity programs identified using the methods.