DEC1/STRA13/SHARP2 and DEC2/SHARP1 coordinate physiological processes, including circadian rhythms in response to environmental stimuli.

Daily physiological and behavioral rhythms are regulated by endogenous circadian molecular clocks. Clock proteins DEC1 (BHLHe40) and DEC2 (BHLHe41) belong to the basic helix-loop-helix protein superfamily, which contains other clock proteins CLOCK and BMAL1. DEC1 and DEC2 are induced by CLOCK:BMAL1 heterodimer via the CACGTG E-box in the promoter and, thereafter, suppress their own expression by competing with CLOCK:BMAL1 for the DNA binding. This negative feedback DEC loop together with the PER loop involving PER and CRY, the other negative clock regulators, maintains the circadian rhythm of Dec1 and Dec2 expression. DEC1 is induced by light pulse and adjusts the circadian phase of the central clock in the suprachiasmatic nucleus, whereas DEC1 upregulation by TGF-β resets the circadian phase of the peripheral clocks in tissues. Furthermore, DEC1 and DEC2 modulate the clock output signals to control circadian rhythms in behavior and metabolism. In addition to the functions in the clocks, DEC1 and DEC2 are involved in hypoxia responses, immunological reactions, and carcinogenesis. These DEC actions are mediated by the direct binding to the E-box elements in target genes or by protein-protein interactions with transcription factors such as HIF-1α, RXRα, MyoD, and STAT. Notably, numerous growth factors, hormones, and cytokines, along with ionizing radiation and DNA-damaging agents, induce Dec1 and/or Dec2 in a tissue-specific manner. These findings suggest that DEC1 and DEC2 play a critical role in animal adaptation to various environmental stimuli.