European journal of biochemistryNov 25, 2004

Role of the DEC1 protein and its interaction with BMAL1 in controlling the body’s daily rhythm

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 30, 2026

Abstract

The N-terminal region of DEC1 is essential for its suppressive activity in circadian rhythm regulation.

DEC1 is expressed in a circadian manner in the suprachiasmatic nucleus, influencing the mammalian circadian rhythm.
It suppresses the CLOCK/BMAL1-activated promoter, with the interaction between DEC1 and BMAL1 being a key molecular mechanism.
The basic helix-loop-helix domain of DEC1 is crucial for its suppressive activity and interaction with BMAL1.
A conserved amino acid, Arg65, in the basic region is required for DEC1's suppression and binding to E-boxes.
Mutations in DEC1 can alter its E-box binding activity without affecting its interaction with BMAL1.
DEC1 can act in a dominant-negative manner, counteracting the suppressive effects of DEC2.

Simplified

The basic helix-loop-helix transcription factor DEC1 is expressed in a circadian manner in the suprachiasmatic nucleus where it seems to play a role in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoter. The interaction of DEC1 with BMAL1 has been suggested as one of the molecular mechanisms of the suppression [Honma, S., Kawamoto, T., Takagi, Y., Fujimoto, K., Sato, F., Noshiro, M., Kato, Y. & Honma, K. (2002) Nature 419, 841-844]. Deletion analysis of DEC1 demonstrated that its N-terminal region, which includes the basic helix-loop-helix domain, was essential for both the suppressive activity and the interaction with BMAL1, as DEC1 lacking the basic region did not show any suppression or interaction. Furthermore, we found that Arg65 in the basic region, which is conserved among group B basic helix-loop-helix proteins, was responsible for the suppression, for the interaction with BMAL1 and for its binding to CACGTG E-boxes. However, substitution of His57 for Ala significantly reduced the E-box binding activity of DEC1, although it did not affect the interaction with BMAL1 or suppression of CLOCK/BMAL1-induced transcription. On the other hand, the basic region-deleted DEC1 acted in a dominant-negative manner for DEC1 activity, indicating that the basic region was not required for homodimer formation of DEC1. Moreover, mutant DEC1 also counteracted DEC2-mediated suppressive activity in a dominant-negative manner. The heterodimer formation of DEC1 and DEC2 was confirmed by pull-down assay. These findings suggest that the basic region of DEC1 participates in the transcriptional regulation through a protein-protein interaction with BMAL1 and DNA binding to the E-box.

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Role of the DEC1 protein and its interaction with BMAL1 in controlling the body’s daily rhythm

Abstract

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