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• W2164826856 endingPage "1369" @default.
• W2164826856 startingPage "1360" @default.
• W2164826856 abstract "The basic helix-loop-helix proteins differentiated embryo chondrocyte 1 (DEC1) and DEC2 are involved in circadian rhythm control. Because the metabolism of dietary nutrients has been linked to circadian regulation, we examined the effect of DEC1 and DEC2 on the function of the metabolite-sensing nuclear receptors, ligand-dependent transcription factors, including retinoid X receptor (RXR) and liver X receptor (LXR). Transfection assays showed that DEC1 and DEC2 repressed ligand-dependent transactivation by RXR. Knockdown of endogenous DEC1 and DEC2 expression with small interfering RNAs augmented ligand-dependent RXRα transactivation. DEC1 and DEC2 interacted directly with RXRα, and ligand addition enhanced their association. DEC1 and DEC2 modified interaction of RXRα with cofactor proteins. Transfection assays using DEC1 and DEC2 mutants revealed that the C-terminal region of DEC2 is required for repression and that an LXXLL motif in DEC1 and DEC2 is necessary for RXRα repression. DEC1 and DEC2 repressed the induction of LXR target genes, associated with the promoter of an LXR target gene, and dissociated from the promoter with ligand treatment. Knockdown of endogenous DEC1 and DEC2 enhanced the LXR target gene expression in hepatocytes. Expression of <i>Dec1</i>, <i>Dec2</i>, and <i>Srebp-1c</i> showed a circadian rhythm in the liver of mice, whereas that of <i>Lxr</i>α, <i>Lxr</i>β, and <i>Rxr</i>α was not rhythmic. DEC1 and DEC2 also repressed the transactivation of other RXR heterodimers, such as farnesoid X receptor, vitamin D receptor, and retinoic acid receptor. Thus, the repressor function of DEC1 and DEC2 may be extended to other RXR heterodimer nuclear receptors." @default.
• W2164826856 created "2016-06-24" @default.
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• W2164826856 date "2009-09-28" @default.
• W2164826856 modified "2023-10-15" @default.
• W2164826856 title "The Basic Helix-Loop-Helix Proteins Differentiated Embryo Chondrocyte (DEC) 1 and DEC2 Function as Corepressors of Retinoid X Receptors" @default.
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• W2164826856 doi "https://doi.org/10.1124/mol.109.057000" @default.
• W2164826856 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19786558" @default.
• W2164826856 hasPublicationYear "2009" @default.
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