| First Author | Stashi E | Year | 2014 |
| Journal | Cell Rep | Volume | 6 |
| Issue | 4 | Pages | 633-45 |
| PubMed ID | 24529706 | Mgi Jnum | J:215957 |
| Mgi Id | MGI:5607392 | Doi | 10.1016/j.celrep.2014.01.027 |
| Citation | Stashi E, et al. (2014) SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm. Cell Rep 6(4):633-45 |
| abstractText | 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. |
