| First Author | Zhang Y | Year | 2015 |
| Journal | Science | Volume | 348 |
| Issue | 6242 | Pages | 1488-92 |
| PubMed ID | 26044300 | Mgi Jnum | J:223370 |
| Mgi Id | MGI:5648743 | Doi | 10.1126/science.aab3021 |
| Citation | Zhang Y, et al. (2015) GENE REGULATION. Discrete functions of nuclear receptor Rev-erbalpha couple metabolism to the clock. Science 348(6242):1488-92 |
| abstractText | Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbalpha, a transcription factor (TF) that functions both as a core repressive component of the cell-autonomous clock and as a regulator of metabolic genes. Here, we show that Rev-erbalpha modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbalpha to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbalpha regulates metabolic genes primarily by recruiting the HDAC3 co-repressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbalpha and ROR TFs provides a universal mechanism for self-sustained control of the molecular clock across all tissues, whereas Rev-erbalpha uses lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. |
