Jmjd3-Mediated H3K27me3 Dynamics Orchestrate Brown Fat Development and Regulate White Fat Plasticity.
Jmjd3-Mediated H3K27me3 Dynamics Orchestrate Brown Fat Development and Regulate White Fat Plasticity.
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DOI：
10.1016/j.devcel.2015.11.002
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发表时间：
2015-12-07
影响因子：
11.8
通讯作者：
Wang YX
中科院分区：
文献类型：
--
作者：
Pan D;Huang L;Zhu LJ;Zou T;Ou J;Zhou W;Wang YX
从棕色前脂肪细胞到脂肪细胞的进展涉及两个转录程序：棕色脂肪（BAT）和白色脂肪（WAT）共同的成脂基因的表达，以及BAT选择性基因的表达。然而，染色质状态和表观遗传酶的动态仍然知之甚少。在这里，我们表明，BAT的发展是有选择地标记和抑制H3 K27 me 3的指导下，并执行其去甲基化酶Jmjd 3。我们发现，一个显着的BAT-选择性基因，但不是常见的脂肪基因或瓦特-选择性基因的子集，在棕色和白色前脂肪细胞划分为H3 K27 me 3。Jmjd 3催化去除H3 K27 me 3，部分通过Rreb 1介导的招聘，是必需的BAT选择性基因的表达和米色脂肪细胞在体外和体内的发展。此外，获得和丧失功能的Jmjd 3转基因小鼠分别表现出年龄依赖性体重减轻和冷耐受性。总之，我们确定了一个表观遗传机制管理BAT的命运决定和WAT可塑性。
Progression from brown preadipocytes to adipocytes engages two transcriptional programs: the expression of adipogenic genes common to both brown fat (BAT) and white fat (WAT), and the expression of BAT-selective genes. However, the dynamics of chromatin states and epigenetic enzymes involved remain poorly understood. Here we show that BAT development is selectively marked and guided by repressive H3K27me3, and is executed by its demethylase Jmjd3. We find that a significant subset of BAT-selective genes, but not common fat genes or WAT-selective genes, are demarcated by H3K27me3 in both brown and white preadipocytes. Jmjd3-catalyzed removal of H3K27me3, in part through Rreb1-mediated recruitment, is required for expression of BAT-selective genes and for development of beige adipocytes both in vitro and in vivo. Moreover, gain- and loss-of-function Jmjd3 transgenic mice show age-dependent body weight reduction and cold intolerance, respectively. Together, we identify an epigenetic mechanism governing BAT fate determination and WAT plasticity.