Novel insights into histone modifiers in adipogenesis.
Novel insights into histone modifiers in adipogenesis.
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DOI：
10.4161/adip.25731
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发表时间：
2013-10-01
期刊：
影响因子：
3.3
通讯作者：
Imai Y
中科院分区：
文献类型：
--
作者：
Okuno Y;Inoue K;Imai Y
近年来，人们逐渐认识到基因表达受组蛋白甲基化状态的调控，而组蛋白甲基化状态又受到组蛋白甲基转移酶（HMTs）和组蛋白去甲基化酶（HDMs）的动态调控。在过去的十年中，许多HMT和HDM被鉴定，其生物学和生化功能已被表征。与其他细胞一样，已知几种HMT和HDM对于从间充质干细胞适当分化成脂肪细胞是必不可少的。Phf 2是最近鉴定的二甲基化组蛋白H3赖氨酸9（H3 K9 me 2）脱甲基酶，其在体外肝细胞和巨噬细胞中具有重要功能;然而，Phf 2的体内意义尚不清楚。为了确定Phf 2的生理作用，我们最近产生了Phf 2敲除小鼠。我们对这些小鼠的分析表明，Phf 2通过共激活CEBPA（脂肪生成的主要调节因子之一），通过其对H3 K9 me 2的去甲基化活性，在脂肪生成中起积极作用。在这篇评论中，我们讨论了几个剩余的问题，在我们的调查Phf 2基因敲除小鼠的表型异常的基础。这些研究与组蛋白修饰剂的新功能有关，可能有助于确定代谢综合征的新治疗靶点。
Recently, it has been progressively recognized that gene expression is regulated by histone methylation status, which is dynamically modulated by histone methyltransferases (HMTs) and histone demethylases (HDMs). In the past decade, many HMTs and HDMs were identified and their biological and biochemical functions have been characterized. As with other cells, several HMTs and HDMs are known to be indispensable for appropriate differentiation of adipocytes from mesenchymal stem cells. Phf2 is a recently identified dimethylated histone H3 lysine 9 (H3K9me2) demethylase that has a significant function in hepatocytes and macrophages in vitro; however, the in vivo significance of Phf2 remains unclear. To determine the physiological role of Phf2, we recently generated Phf2 knockout mice. Our analyses of these mice revealed that Phf2 has a positive role in adipogenesis by coactivating CEBPA, one of the master regulators of adipogenesis, through its demethylation activity toward H3K9me2. In this commentary, we discuss several remaining questions that underlie phenotypic abnormalities seen in our investigations of Phf2 knockout mice. These studies are related to novel functions of histone modifiers and may help identify new therapeutic targets for metabolic syndrome.