Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells.
Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells.
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MiR-214依赖性调节骨骼肌和胚胎干细胞中Polycomb蛋白EZH2的调节。
DOI：
10.1016/j.molcel.2009.08.008
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发表时间：
2009-10-09
期刊：
影响因子：
16
通讯作者：
Sartorelli, Vittorio
中科院分区：
文献类型：
--
作者：
Juan, Aster H.;Kumar, Roshan M.;Marx, Joseph G.;Young, Richard A.;Sartorelli, Vittorio
多梳族 (PcG) 蛋白在最不同的生物过程中发挥重要功能。 PcG 蛋白对细胞定型和分化的贡献与其抑制胚胎干 (ES) 细胞和定型细胞谱系（包括骨骼肌细胞 (SMC)）中发育调节因子转录的能力有关。 PcG 蛋白优先从转录区域去除，但潜在机制仍不清楚。在这里，PcG 蛋白被发现占据并抑制未分化 SMC 中含有 microRNA miR-214 的内含子区域的转录。细胞分化与 PcG 脱离、发育调节因子 MyoD 和肌细胞生成素的募集以及 miR-214 转录的激活同时发生。转录后，miR-214 通过靶向 Ezh2 3'UTR（PRC2 复合物的催化亚基）对 PcG 进行负反馈。 miR-214 介导的 Ezh2 蛋白减少可加速 SMC 分化并促进 ES 细胞中发育调节因子的非计划转录。因此，miR-214 和 Ezh2 建立了一个调节环，控制细胞分化过程中 PcG 依赖性基因的表达。
Polycomb group (PcG) proteins exert essential functions in the most disparate biological processes. The contribution of PcG proteins to cell commitment and differentiation relates to their ability to repress transcription of developmental regulators in embryonic stem (ES) cells and in committed cell lineages, including skeletal muscle cells (SMC). PcG proteins are preferentially removed from transcribed regions but the underlying mechanisms remain unclear. Here, PcG proteins are found to occupy and repress transcription from an intronic region containing the microRNA miR-214 in undifferentiated SMC. Cell differentiation coincides with PcG disengagement, recruitment of the developmental regulators MyoD and myogenin, and activation of miR-214 transcription. Once transcribed, miR-214 negatively feeds back on PcG by targeting the Ezh2 3′UTR, the catalytic subunit of the PRC2 complex. miR-214-mediated Ezh2 protein reduction accelerates SMC differentiation and promotes unscheduled transcription of developmental regulators in ES cells. Thus, miR-214 and Ezh2 establish a regulatory loop controlling PcG-dependent gene expression during cell differentiation.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
64.5
作者：
Guenther, Matthew G.;Levine, Stuart S.;Young, Richard A.
通讯作者：
Young, Richard A.
影响因子：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA
影响因子：
5.3
作者：
Haberland, Michael;Arnold, Michael A.;Olson, Eric N.
通讯作者：
Olson, Eric N.
影响因子：
4.4
作者：
Loebel, DAF;Tsoi, B;Tam, PPL
通讯作者：
Tam, PPL