A Circadian Rhythm Orchestrated by Histone Deacetylase 3 Controls Hepatic Lipid Metabolism

被引：602

作者：

Feng, Dan ^{[1
,2
]}

Liu, Tao ^{[3
,4
]}

Sun, Zheng ^{[1
,2
]}

Bugge, Anne ^{[1
,2
]}

Mullican, Shannon E. ^{[1
,2
]}

Alenghat, Theresa ^{[1
,2
]}

Liu, X. Shirley ^{[3
,4
]}

Lazar, Mitchell A. ^{[1
,2
]}

机构：

[1] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Dept Med,Dept Genet, Philadelphia, PA 19104 USA

[2] Univ Penn, Sch Med, Inst Diabet Obes & Metab IDOM, Philadelphia, PA 19104 USA

[3] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

来源：

SCIENCE | 2011年 / 331卷 / 6022期

关键词：

RECEPTOR COREPRESSOR; TRANSCRIPTION; LIVER; CLOCK; MICE; TISSUE;

D O I：

10.1126/science.1198125

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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

引用

页码：1315 / 1319

页数：5

共 30 条

[1]

Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology [J].