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


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

SUBMITTER: Feng D 

PROVIDER: S-EPMC3389392 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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

Feng Dan D   Liu Tao T   Sun Zheng Z   Bugge Anne A   Mullican Shannon E SE   Alenghat Theresa T   Liu X Shirley XS   Lazar Mitchell A MA  

Science (New York, N.Y.) 20110301 6022


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 HDA  ...[more]

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