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Nature:脂肪细胞命运的控制

来源:Nature中文网 2013-12-05 09:38

这项研究表明,棕色脂肪组织中含量较高的一种名为“euchromatic histone-lysine N-methyltransferase 1 (EHMT1)”的酶是控制棕色脂肪细胞命运的PRDM16转录复合物的一个必要成分。

棕色脂肪细胞中EHMT1的丢失导致棕色脂肪特点的丧失,在活体中通过肌肉选择性基因启动子的“Histone 3 Lys 9”的脱甲基化诱导肌肉分化。

相比之下,EHMT1表达通过使PRDM16蛋白稳定来打开棕色脂肪细胞中的生热基因程序。将EHMT1从脂肪中删除,会减少由BAT介导的适应性热生成,造成肥胖和胰岛素抗性。(生物谷Bioon.com)

生物谷推荐的英文摘要

Nature            doi:10.1038/nature12652

EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex

Haruya Ohno,Kosaku Shinoda,Kana Ohyama,Louis Z. Sharp& Shingo Kajimura

Brown adipose tissue (BAT) dissipates chemical energy in the form of heat as a defence against hypothermia and obesity. Current evidence indicates that brown adipocytes arise from Myf5+ dermotomal precursors through the action of PR domain containing protein 16 (PRDM16) transcriptional complex1, 2. However, the enzymatic component of the molecular switch that determines lineage specification of brown adipocytes remains unknown. Here we show that euchromatic histone-lysine N-methyltransferase 1 (EHMT1) is an essential BAT-enriched lysine methyltransferase in the PRDM16 transcriptional complex and controls brown adipose cell fate. Loss of EHMT1 in brown adipocytes causes a severe loss of brown fat characteristics and induces muscle differentiation in vivo through demethylation of histone 3 lysine 9 (H3K9me2 and 3) of the muscle-selective gene promoters. Conversely, EHMT1 expression positively regulates the BAT-selective thermogenic program by stabilizing the PRDM16 protein. Notably, adipose-specific deletion of EHMT1 leads to a marked reduction of BAT-mediated adaptive thermogenesis, obesity and systemic insulin resistance. These data indicate that EHMT1 is an essential enzymatic switch that controls brown adipose cell fate and energy homeostasis.

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