title: Regulation of basic helix-loop-helix transcription factors Dec1 and Dec2 by RORα and their roles in adipogenesis.
abstract: 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.
authors.affiliation: Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Ozaki
authors.forename: Mitsuhide
authors.initials: M
authors.lastname: Noshiro
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.forename: Kiyomasa
authors.initials: K
authors.lastname: Honda
authors.forename: Urara
authors.initials: U
authors.lastname: Fukuzaki-Dohi
authors.forename: Sato
authors.initials: S
authors.lastname: Honma
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Kotaro
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001665:Binding Sites; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023061:Gene Order; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D014157:Transcription Factors; C538961:Bmal1 protein, mouse; C470968:Bhlhb3 protein, mouse; C491539:Bhlhe40 protein, mouse; C539739:Rora protein, mouse