Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation
Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation
复制标题
DOI：
10.1016/j.devcel.2004.10.005
复制
发表时间：
2004-11-01
影响因子：
11.8
通讯作者：
Brockdorff, N
中科院分区：
文献类型：
--
作者：
de Napoles, M;Mermoud, JE;Brockdorff, N
在许多高等生物中，5%-15%的组蛋白H2 A在赖氨酸119（uH 2A）处被泛素化。然而，这种修改的功能及其建立所涉及的因素尚不清楚。在这里，我们表明，uH 2A发生在女性哺乳动物的非活性X染色体，这与招聘的Polycomb组（PcG）蛋白属于Polycomb阻遏复合物1（PRC 1）。基于我们的观察，我们测试了PRC 1蛋白Ring 1B及其密切相关的同系物Ring 1A在H2 A泛素化中的作用。Ring 1B无效胚胎干细胞（ES）的分析揭示了广泛的全球uH 2A水平的耗竭。在失活的X染色体上，uH 2A维持在Ring 1A或Ring 1B无效细胞中，但不在双敲除细胞中，表明这些蛋白质在发育中的重叠功能。这些观察结果将H2 A泛素化、X失活和PRC 1 PcG功能联系起来，提示了染色质介导的可遗传基因沉默的一种意想不到的新机制。
In many higher organisms, 5%-15% of histone H2A is ubiquitylated at lysine 119 (uH2A). The function of this modification and the factors involved in its establishment, however, are unknown. Here we demonstrate that uH2A occurs on the inactive X chromosome in female mammals and that this correlates with recruitment of Polycomb group (PcG) proteins belonging to Polycomb repressor complex 1 (PRC1). Based on our observations, we tested the role of the PRC1 protein Ring1B and its closely related homolog Ring1A in H2A ubiquitylation. Analysis of Ring1B null embryonic stem (ES) cells revealed extensive depletion of global uH2A levels. On the inactive X chromosome, uH2A was maintained in Ring1A or Ring1B null cells, but not in double knockout cells, demonstrating an overlapping function for these proteins in development. These observations link H2A ubiquitylation, X inactivation, and PRC1 PcG function, suggesting an unanticipated and novel mechanism for chromatin-mediated heritable gene silencing.