SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm.
Cell Rep
; 6(4): 633-45, 2014 Feb 27.
Article
in En
| MEDLINE
| ID: mdl-24529706
Synchrony of the mammalian circadian clock is achieved by complex transcriptional and translational feedback loops centered on the BMAL1:CLOCK heterodimer. Modulation of circadian feedback loops is essential for maintaining rhythmicity, yet the role of transcriptional coactivators in driving BMAL1:CLOCK transcriptional networks is largely unexplored. Here, we show diurnal hepatic steroid receptor coactivator 2 (SRC-2) recruitment to the genome that extensively overlaps with the BMAL1 cistrome during the light phase, targeting genes that enrich for circadian and metabolic processes. Notably, SRC-2 ablation impairs wheel-running behavior, alters circadian gene expression in several peripheral tissues, alters the rhythmicity of the hepatic metabolome, and deregulates the synchronization of cell-autonomous metabolites. We identify SRC-2 as a potent coregulator of BMAL1:CLOCK and find that SRC-2 targets itself with BMAL1:CLOCK in a feedforward loop. Collectively, our data suggest that SRC-2 is a transcriptional coactivator of the BMAL1:CLOCK oscillators and establish SRC-2 as a critical positive regulator of the mammalian circadian clock.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Circadian Rhythm
/
Nuclear Receptor Coactivator 2
/
Metabolome
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2014
Document type:
Article
Affiliation country:
Country of publication: