A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism
Year: 2011
Type: article
Abstract: 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-erbα. Rev-erbα colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbα in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.
Source: Science
Authors: Dan Feng, Tao Liu, Zheng Sun, Anne Bugge, Shannon E. Mullican, Theresa Alenghat, X. Shirley Liu, Mitchell A. Lazar
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: G1073058310, G1790515647, G2158526501, Biology of REV-ERB nuclear receptors, Computational Models for Mechanisms of Global Transcription, Integrative Metabolic Adaptations to Enviromental and Nutritional Challenge, Genome-wide epigenetic control of circadian metabolism by heme receptor Rev-erb, Thyroid hormone receptors - regulation and function, Integrative Physiology of Thyroid Hormone Receptors and Nuclear Receptor Corepressors, University of Pennsylvania Diabetes Research Center
OpenAlex ID: W1998585946