RRC ID 38211
Author Akashi M, Takumi T.
Title The orphan nuclear receptor RORalpha regulates circadian transcription of the mammalian core-clock Bmal1.
Journal Nat Struct Mol Biol
Abstract The PAS (PER-ARNT-SIM) helix-loop-helix transcription factor BMAL1 (also known as MOP3) is an essential component of the circadian pacemaker in mammals. Here we show that the retinoic acid receptor-related orphan receptor RORalpha (NR1F1) directly activates transcription of Bmal1 through two conserved RORalpha response elements that are required for cell-autonomous transcriptional oscillation of Bmal1 mRNA. Positive involvement of RORalpha in generation of the Bmal1 circadian oscillation was verified by behavioral analyses of RORalpha-deficient staggerer mice that showed aberrant locomotor activity and unstable rhythmicity. In cultured cells, loss of endogenous RORalpha protein resulted in a dampened circadian rhythm of Bmal1 transcription, further indicating that RORalpha is a functional component of the cell-autonomous core circadian clock. These results indicate that RORalpha acts to promote Bmal1 transcription, thereby maintaining a robust circadian rhythm.
Volume 12(5)
Pages 441-8
Published 2005-5-1
DOI 10.1038/nsmb925
PII nsmb925
PMID 15821743
MeSH ARNTL Transcription Factors Animals Basic Helix-Loop-Helix Transcription Factors Behavior, Animal / physiology Cell Line Circadian Rhythm / genetics* Circadian Rhythm / physiology* DNA / genetics DNA / metabolism Gene Expression Regulation* Mice Mutation / genetics Nuclear Receptor Subfamily 1, Group F, Member 1 Promoter Regions, Genetic / genetics RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Cytoplasmic and Nuclear / deficiency Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Response Elements / genetics Trans-Activators / deficiency Trans-Activators / genetics Trans-Activators / metabolism* Transcription Factors / genetics* Transcription, Genetic / genetics*
IF 11.98
Times Cited 273
DNA material pcDNA3-hROR alpha 1 (RDB14169) pcDNA3-hROR alpha 1-delta LBD (RDB14170) pcDNA3-hROR alpha 4 (RDB14171) pcDNA3-hROR beta (RDB14172) pcDNA3-hROR gamma (RDB14173) pGL3_hBmalPro-Luc (-3465_Full) (RDB14174) pGL3_hBmalPro-Luc (-2442_+57) (RDB14175) pGL3_hBmalPro-Luc (-1579_+57) (RDB14176) pGL3_hBmalPro-Luc (-829_+57) (RDB14177) pGL3_hBmalPro-Luc (-481_+57) (RDB14178) pGL3_hBmalPro-Luc (-230_+57) (RDB14179) pGL3_hBmalPro-Luc (-829 E1 mut/E2) (RDB14180) pGL3_hBmalPro-Luc (-829 E1 /E2 mut) (RDB14181) pGL3_hBmalPro-Luc(-829 E1 mut/E2 mut) (RDB14182) pcDNA3-mREV-erb alpha (RDB14183) pcDNA3-mREV-erb beta (RDB14184).