RRC ID |
38211
|
著者 |
Akashi M, Takumi T.
|
タイトル |
The orphan nuclear receptor RORalpha regulates circadian transcription of the mammalian core-clock Bmal1.
|
ジャーナル |
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.
|
巻・号 |
12(5)
|
ページ |
441-8
|
公開日 |
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
|
引用数 |
273
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
遺伝子材料 |
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). |