MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation.
MicroRNA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation.
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DOI：
10.1016/j.stem.2011.12.004
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发表时间：
2012-01-06
期刊：
影响因子：
23.9
通讯作者：
Gil, Jesus
中科院分区：
文献类型：
--
作者：
O'Loghlen, Ana;Munoz-Cabello, Ana M.;Gaspar-Maia, Alexandre;Wu, Hsan-Au;Banito, Ana;Kunowska, Natalia;Racek, Tomas;Pemberton, Helen N.;Beolchi, Patrizia;Lavial, Fabrice;Masui, Osamu;Vermeulen, Michiel;Carroll, Thomas;Graumann, Johannes;Heard, Edith;Dillon, Niall;Azuara, Veronique;Snijders, Ambrosius P.;Peters, Gordon;Bernstein, Emily;Gil, Jesus
染色质修饰剂的Polycomb Group（PcG）调节多能性和分化。哺乳动物基因组编码Polycomb抑制复合物1（PRC 1）组分的多个同源物，包括果蝇Polycomb蛋白的五个直系同源物（Cbx 2，Cbx 4，Cbx 6，Cbx 7和Cbx 8）。我们已经确定Cbx 7作为PRC 1复合物在胚胎干细胞（ESC）的主要Polycomb直系同源物。在ESC分化过程中，Cbx 7的表达下调，先于Cbx 2、Cbx 4和Cbx 8的上调，而Cbx 2、Cbx 4和Cbx 8直接受Cbx 7抑制。Cbx 7的异位表达抑制分化和X染色体失活并增强ESC自我更新相反，Cbx 7敲低诱导分化和去抑制谱系特异性标志物。在功能筛选中，我们鉴定了miR-125和miR-181家族作为在ESC分化期间诱导的Cbx 7的调节剂。这些miRNAs的异位表达通过调控Cbx 7加速ESC分化。这些观察结果确立了Cbx 7及其调控miRNA在决定多能性中的关键作用。Cbx 7是多能细胞中PRC 1复合物的主要Pc直系同源物，Cbx 7在ESC分化过程中抑制其同源物以调节PRC 1组成，Cbx 7通过抑制分化促进干细胞样状态，miR-181和miR-125在ESC分化过程中调节Cbx 7表达。
The Polycomb Group (PcG) of chromatin modifiers regulates pluripotency and differentiation. Mammalian genomes encode multiple homologs of the Polycomb repressive complex 1 (PRC1) components, including five orthologs of the Drosophila Polycomb protein (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8). We have identified Cbx7 as the primary Polycomb ortholog of PRC1 complexes in embryonic stem cells (ESCs). The expression of Cbx7 is downregulated during ESC differentiation, preceding the upregulation of Cbx2, Cbx4, and Cbx8, which are directly repressed by Cbx7. Ectopic expression of Cbx7 inhibits differentiation and X chromosome inactivation and enhances ESC self-renewal. Conversely, Cbx7 knockdown induces differentiation and derepresses lineage-specific markers. In a functional screen, we identified the miR-125 and miR-181 families as regulators of Cbx7 that are induced during ESC differentiation. Ectopic expression of these miRNAs accelerates ESC differentiation via regulation of Cbx7. These observations establish a critical role for Cbx7 and its regulatory miRNAs in determining pluripotency. ► Cbx7 is the primary Pc ortholog of the PRC1 complex in pluripotent cells ► Cbx7 repress its homologs to regulate PRC1 composition during ESC differentiation ► Cbx7 promotes a stem-cell-like state by repressing differentiation ► miR-181 and miR-125 regulate Cbx7 expression during ESC differentiation
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影响因子：
64.5
作者：
Masui O;Bonnet I;Le Baccon P;Brito I;Pollex T;Murphy N;Hupé P;Barillot E;Belmont AS;Heard E
通讯作者：
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Wutz, Anton
影响因子：
2.2
作者：
Glud, Martin;Manfe, Valentina;Gniadecki, Robert
通讯作者：
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影响因子：
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作者：
Marson A;Levine SS;Cole MF;Frampton GM;Brambrink T;Johnstone S;Guenther MG;Johnston WK;Wernig M;Newman J;Calabrese JM;Dennis LM;Volkert TL;Gupta S;Love J;Hannett N;Sharp PA;Bartel DP;Jaenisch R;Young RA
通讯作者：
Young RA
MiR-214依赖性调节骨骼肌和胚胎干细胞中Polycomb蛋白EZH2的调节。
影响因子：
16
作者：
Juan, Aster H.;Kumar, Roshan M.;Marx, Joseph G.;Young, Richard A.;Sartorelli, Vittorio
通讯作者：
Sartorelli, Vittorio