Regulation of basic helix‐loop‐helix transcription factors Dec1 and Dec2 by RORα and their roles in adipogenesis

• Published in: Genes to cells : devoted to molecular & cellular mechanisms Vol. 17; no. 2; pp. 109 - 121
• Main Authors: Ozaki, Noritsugu, Noshiro, Mitsuhide, Kawamoto, Takeshi, Nakashima, Ayumu, Honda, Kiyomasa, Fukuzaki‐Dohi, Urara, Honma, Sato, Fujimoto, Katsumi, Tanimoto, Kotaro, Tanne, Kazuo, Kato, Yukio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012
• Subjects: Adipocytes; adipogenesis; Adipogenesis - genetics; Animals; ARNTL Transcription Factors - genetics; Base Sequence; Basic Helix-Loop-Helix Transcription Factors - genetics; Binding Sites; BMAL1 protein; Cell Line; Chromatin; Circadian Rhythm - genetics; Circadian rhythms; CLOCK protein; Differentiation; Electrophoretic mobility; Gene Expression Profiling; Gene Expression Regulation; Gene Order; Helix-loop-helix proteins; Homeodomain Proteins - genetics; Immunoprecipitation; Male; Metabolism; Mice; Mice, Inbred C57BL; Nuclear Receptor Subfamily 1, Group F, Member 1 - metabolism; Nuclear receptors; Pacemakers; Promoter Regions, Genetic; Promoters; Regulatory sequences; Repressors; Response Elements; Suprachiasmatic nucleus; Transcription factors; Transcription Factors - genetics
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/j.1365-2443.2011.01574.x

DEC1 and DEC2, members of the basic helix‐loop‐helix superfamily, are involved in various biological phenomena including clock systems, cell differentiation and metabolism. In clock systems, Dec1 and Dec2 expression are up‐regulated by the CLOCK:BMAL1 heterodimer via E‐box (CACGTG), exhibiting a circadian rhythm in the suprachiasmatic nucleus (SCN), the central circadian pacemaker and other peripheral tissues. In this study, using assays of luciferase reporters, electrophoretic mobility shift and chromatin immunoprecipitation, we identified novel nuclear receptor response elements, ROR response elements (RORE), in Dec1 and Dec2 promoters. These ROREs responded to the transcriptional activator RORα, but not to the repressor REVERBα, although the Bmal1 promoter responded to both RORα and REVERBα. Therefore, RORα, but not REVERBα, is involved in the regulation of Dec1 and Dec2 expression without significantly affecting their rhythmicity. Since RORα, DEC1 and DEC2 reportedly suppressed adipogenic differentiation, we examined expression of Rorα, Dec1, Dec2 and other clock‐controlled genes in differentiating 3T3‐L1 adipocytes. The results suggested that RORα suppresses adipogenic differentiation at a later stage of differentiation by RORE‐mediated stimulation of Dec1 and Dec2 expression.