First Author | Feng D | Year | 2011 |
Journal | Science | Volume | 331 |
Issue | 6022 | Pages | 1315-9 |
PubMed ID | 21393543 | Mgi Jnum | J:169669 |
Mgi Id | MGI:4941643 | Doi | 10.1126/science.1198125 |
Citation | Feng D, et al. (2011) A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism. Science 331(6022):1315-9 |
abstractText | Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erbalpha. Rev-erbalpha colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbalpha in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbalpha directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis. |