A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism

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-erba. Rev-erba colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erba in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erba directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.