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Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism
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Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism
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Journal Article
Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism
2011
Overview
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.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Animals
/ Biological and medical sciences
/ Chromatin Immunoprecipitation
/ Chronobiology Disorders - genetics
/ Chronobiology Disorders - metabolism
/ Diabetes
/ Fundamental and applied biological sciences. Psychology
/ genes
/ Genome
/ Genomes
/ Genomics
/ Histone Deacetylases - metabolism
/ Histones
/ Lipids
/ Liver
/ Metabolisms and neurohumoral controls
/ Mice
/ Nuclear Receptor Co-Repressor 1 - metabolism
/ Nuclear Receptor Subfamily 1, Group D, Member 1 - genetics
/ Nuclear Receptor Subfamily 1, Group D, Member 1 - metabolism
/ Obesity
/ RNA Polymerase II - metabolism
/ Vertebrates: anatomy and physiology, studies on body, several organs or systems
