A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism.
A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism.
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DOI：
10.1126/science.1198125
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发表时间：
2011-03-11
期刊：
影响因子：
--
通讯作者：
Lazar MA
中科院分区：
文献类型：
--
作者：
Feng D;Liu T;Sun Z;Bugge A;Mullican SE;Alenghat T;Liu XS;Lazar MA
生物钟的紊乱会加剧包括肥胖和糖尿病在内的代谢性疾病。在此我们表明，组蛋白去乙酰化酶3（HDAC3）在小鼠肝脏基因组上的募集呈现出一种昼夜节律。组蛋白乙酰化与HDAC3的结合呈负相关，并且当HDAC3缺失时，这种节律就会消失。尽管HDAC3的量是恒定的，但其在肝脏基因组上的募集与昼夜节律核受体Rev - erbα的表达模式相符。Rev - erbα与HDAC3在调控脂质代谢的基因附近共定位，并且在小鼠肝脏中HDAC3或Rev - erbα的缺失会导致肝脏脂肪变性。因此，Rev - erbα对HDAC3的基因组募集引导了组蛋白乙酰化的昼夜节律以及正常肝脏脂质内稳态所必需的基因表达。
Disruption of the circadian clock exacerbates metabolic diseases including obesity and diabetes. Here 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.
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影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
5.3
作者：
Guenther, MG;Barak, O;Lazar, MA
通讯作者：
Lazar, MA
影响因子：
4.5
作者：
Liu AC;Tran HG;Zhang EE;Priest AA;Welsh DK;Kay SA
通讯作者：
Kay SA
DOI：
10.1073/pnas.0808180106
发表时间：
2009-03-17
影响因子：
11.1
作者：
Scheer, Frank A. J. L.;Hilton, Michael F.;Shea, Steven A.
通讯作者：
Shea, Steven A.
影响因子：
4.3
作者：
Sookoian, Silvia;Castano, Gustavo;Pirola, Carlos Jose
通讯作者：
Pirola, Carlos Jose