Abstract: An object of the present invention is to clarify unelucidated aspects in the control mechanism of circadian rhythms. The present inventors have newly found that ROR? (retinoic acid binding-receptor alpha; the same shall apply hereinafter) stimulates an induction of Bmal1 expression and also that the induction of Bmal1 expression is promoted under hypoxia. These findings strongly suggest the existence of a control mechanism of circadian rhythms that, when ROR? expression is promoted under hypoxia or the like, an induction of Bmal1 expression is stimulated and, when the induction of Bmal1 expression is stimulated, binding between BMAL1 and CLOCK is stimulated and an induction of Per gene or Cry gene expression is stimulated. The present invention, therefore, has applicability as jet-lag regulating agents and anticancer agents.

Abstract: An object of the present invention is to clarify unelucidated aspects in the control mechanism of circadian rhythms. The present inventors have newly found that ROR? (retinoic acid binding-receptor alpha; the same shall apply hereinafter) stimulates an induction of Bmal1 expression and also that the induction of Bmal1 expression is promoted under hypoxia. These findings strongly suggest the existence of a control mechanism of circadian rhythms that, when ROR? expression is promoted under hypoxia or the like, an induction of Bmal1 expression is stimulated and, when the induction of Bmal1 expression is stimulated, binding between BMAL1 and CLOCK is stimulated and an induction of Per gene or Cry gene expression is stimulated. The present invention, therefore, has applicability as jet-lag regulating agents and anticancer agents.

Abstract: The molecular reaction mechanism that associates the clock gene with stress is elucidated based on the finding that stress is accompanied by an increase in the expression level of Per1 gene in peripheral tissues, stress response does not change the circadian rhythm in peripheral tissues, and Per1 gene increases in its expression level dependently on the responsive element of glucocorticoid existing in its promoter region. This finding is used for stress evaluation. That is, stress can be evaluated for its presence or absence or degree by detection and determination of an increase in the transcript (mRNA) of Per1 gene in peripheral tissues (an increase in the protein coded by Per1 gene).

Abstract: A circadian rhythm control gee cluster (Bmal1 gene, Npas2 gene, Rev-erb?, Dbp gene, Per3 gene, Per2 gene and Per1 gene) having a given expression timing and expression sequence under normal conditions is provided along with a DNA chip having, at least, the circadian control gene group sequentially arranged. There are also provided a method for predicting modulation in expression timing of the circadian rhythm control gene cluster, a method for detecting a circadian rhythm modulation, a method for selecting a circadian rhythm regulator, a method for screening a circadian rhythm regulator, and screening of a substance involving modulation of a circadian rhythm as a side effect, each using the DNA chip.

Abstract: A method for inspecting a quality of a sensor chip using either of (1) and (2) indicated below as a judgment index is provided: (1) interrelations of a plurality of circadian rhythm control genes in respect of expression level thereof; and (2) time-lapse patterns of specified circadian rhythm control genes in respect of expression level thereof. A method of evaluating whether sampling and preparation of a sample to be subjected to detection of interaction between substances is proper is also provided wherein (1) or (2) defined above is used as a judgment index. DNA and protein chips useful for the methods are also provided.