09年2月4日在线版的Nature发表了北卡罗莱纳大学医学院生物化学与生物物理学系教授，霍华德·休斯医学研究院(HHMI)研究员张毅教授的一项研究成果：Role of Jhdm2a in regulating metabolic gene expression and obesity resistance。
这篇文章主要聚焦于甲基化研究，文章提到，近年来的研究表明组蛋白甲基转移酶和去甲基酶对于组蛋白甲基化状态影响很大，比如H3K9特异性去甲基化酶Jhdm2a（也称为Jmjd1a和Kdm3a）在细胞核激素受体介导的基因激活，和雄性生殖细胞发育等过程中就扮演了重要角色。
在这篇文章中，研究人员首次提出了Jhdm2a在调控代谢基因表达和正常体重调控方面的重要作用。研究人员发现缺乏Jhdm2a会导致细胞中β－肾上腺素刺激的糖释放和棕色脂肪组织中氧消耗的紊乱，以及降低骨骼肌肉中脂肪氧化和糖释放，而且他们还证明了Jhdm2与Ucp1基因的PPAR应答元件（PPRE）之间的绑定（β－肾上腺素激活诱导）不仅降低了PPRE中H3K9me2的表达水平，而且有利于一些相关因子的补充。
这项研究证明了Jhdm2a在调控代谢基因表达和正常体重调控方面的重要作用，对于未来代谢基因调控和肥胖症的研究具有积极的指导意义。（生物谷Bioon.com）
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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.
