09年2月4日在線版的Nature發(fā)表了北卡羅萊納大學(xué)醫(yī)學(xué)院生物化學(xué)與生物物理學(xué)系教授,，霍華德·休斯醫(yī)學(xué)研究院(HHMI)研究員張毅教授的一項研究成果：Role of Jhdm2a in regulating metabolic gene expression and obesity resistance,。
這篇文章主要聚焦于甲基化研究，文章提到,，近年來的研究表明組蛋白甲基轉(zhuǎn)移酶和去甲基酶對于組蛋白甲基化狀態(tài)影響很大,，比如H3K9特異性去甲基化酶Jhdm2a（也稱為Jmjd1a和Kdm3a）在細(xì)胞核激素受體介導(dǎo)的基因激活，和雄性生殖細(xì)胞發(fā)育等過程中就扮演了重要角色,。
在這篇文章中,，研究人員首次提出了Jhdm2a在調(diào)控代謝基因表達(dá)和正常體重調(diào)控方面的重要作用。研究人員發(fā)現(xiàn)缺乏Jhdm2a會導(dǎo)致細(xì)胞中β－腎上腺素刺激的糖釋放和棕色脂肪組織中氧消耗的紊亂,，以及降低骨骼肌肉中脂肪氧化和糖釋放,，而且他們還證明了Jhdm2與Ucp1基因的PPAR應(yīng)答元件（PPRE）之間的綁定（β－腎上腺素激活誘導(dǎo)）不僅降低了PPRE中H3K9me2的表達(dá)水平，而且有利于一些相關(guān)因子的補充,。
這項研究證明了Jhdm2a在調(diào)控代謝基因表達(dá)和正常體重調(diào)控方面的重要作用,，對于未來代謝基因調(diào)控和肥胖癥的研究具有積極的指導(dǎo)意義。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature , Published online 4 February 2009, doi:10.1038/nature07777
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance
Keisuke Tateishi1,2,3, Yuki Okada1,2, Eric M. Kallin1,2 & Yi Zhang1,2
1 Howard Hughes Medical Institute,
2 Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA
Recent studies indicate that the methylation state of histones can be dynamically regulated by histone methyltransferases and demethylases1, 2. The H3K9-specific demethylase Jhdm2a (also known as Jmjd1a and Kdm3a) has an important role in nuclear hormone receptor-mediated gene activation and male germ cell development3, 4. Through disruption of the Jhdm2a gene in mice, here we demonstrate that Jhdm2a is critically important in regulating the expression of metabolic genes. The loss of Jhdm2a function results in obesity and hyperlipidemia in mice. We provide evidence that the loss of Jhdm2a function disrupts -adrenergic-stimulated glycerol release and oxygen consumption in brown fat, and decreases fat oxidation and glycerol release in skeletal muscles. We show that Jhdm2a expression is induced by -adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor (Ppara) and Ucp1 expression. Furthermore, we demonstrate that -adrenergic activation-induced binding of Jhdm2a to the PPAR responsive element (PPRE) of the Ucp1 gene not only decreases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at the PPRE, but also facilitates the recruitment of Ppar and Rxr and their co-activators Pgc1 (also known as Ppargc1a), CBP/p300 (Crebbp) and Src1 (Ncoa1) to the PPRE. Our studies thus demonstrate an essential role for Jhdm2a in regulating metabolic gene expression and normal weight control in mice.
