Class E basic helix-loop-helix protein 41

Definition:

Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes. Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes. Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).

References:

[1]. Ayumu Nakashima, et al. DEC1 modulates the circadian phase of clock gene expression. Mol Cell Biol. 2008 Jun;28(12):4080-92. [Content Brief]

[2]. Renata Pellegrino, et al. A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans. Sleep. 2014 Aug 1;37(8):1327-36. [Content Brief]

[3]. Takeshi Kawamoto, et al. A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation. Biochem Biophys Res Commun. 2004 Jan 2;313(1):117-24. [Content Brief]

[4]. Fuyuki Sato, et al. Functional analysis of the basic helix-loop-helix transcription factor DEC1 in circadian regulation. Interaction with BMAL1. Eur J Biochem. 2004 Nov;271(22):4409-19. [Content Brief]

[5]. Yuxin Li, et al. DNA binding, but not interaction with Bmal1, is responsible for DEC1-mediated transcription regulation of the circadian gene mPer1. Biochem J. 2004 Sep 15;382(Pt 3):895-904. [Content Brief]

[6]. Yoshitake Cho, et al. The basic helix-loop-helix proteins differentiated embryo chondrocyte (DEC) 1 and DEC2 function as corepressors of retinoid X receptors. Mol Pharmacol. 2009 Dec;76(6):1360-9. [Content Brief]

[7]. M Garriga-Canut, et al. The basic helix-loop-helix protein, sharp-1, represses transcription by a histone deacetylase-dependent and histone deacetylase-independent mechanism. J Biol Chem. 2001 May 4;276(18):14821-8. [Content Brief]

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