Current topics in developmental biologySep 25, 2014

DEC1 and DEC2 proteins work together to control body rhythms and responses to the environment

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

DEC1 and DEC2 proteins are associated with regulating circadian rhythms and responding to environmental stimuli.

DEC1 and DEC2 are clock proteins that are induced by the CLOCK:BMAL1 complex and suppress their own expression in a negative feedback loop.
DEC1 responds to light and can adjust the central circadian clock's phase, while its upregulation by TGF-β influences the phase of peripheral clocks in tissues.
Both DEC1 and DEC2 modulate signals that control circadian rhythms in behavior and metabolism.
DEC1 and DEC2 are involved in responses to low oxygen levels, immune reactions, and cancer development.
Their functions are mediated by direct binding to specific DNA elements or interactions with other transcription factors.
Various factors, including growth factors and DNA-damaging agents, can induce DEC1 and/or DEC2 in a tissue-specific manner.

Simplified

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.

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DEC1 and DEC2 proteins work together to control body rhythms and responses to the environment

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