当前位置: Nature » 蛋白&蛋白质组学 » 正文


摘要 : 在这项研究中,Michael Rosenfeld 及同事发现,组蛋白H2A的球形区域的一个保守的酪氨酸残基Y57被“酪蛋白激酶-2”(CK2)未曾料到的酪氨酸激酶活性磷酸化。

 组蛋白的转录后修饰涉及包括转录在内的各种核过程的调控。在这项研究中,Michael Rosenfeld 及同事发现,组蛋白H2A的球形区域的一个保守的酪氨酸残基Y57被“酪蛋白激酶-2”(CK2)未曾料到的酪氨酸激酶活性磷酸化。



The co<em></em>nserved Tyr 57 residue in H2A is phosphorylated.



Tyrosine phosphorylation of histone H2A by CK2 regulates transcriptional elongation

Harihar Basnet, Xue B. Su, Yuliang Tan, Jill Meisenhelder, Daria Merkurjev, Kenneth A. Ohgi, Tony Hunter, Lorraine Pillus & Michael G. Rosenfeld

Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, DNA replication and DNA damage repair1. The identification of new histone modifications critical for transcriptional regulation at initiation, elongation or termination is of particular interest. Here we report a new layer of regulation in transcriptional elongation that is conserved from yeast to mammals. This regulation is based on the phosphorylation of a highly conserved tyrosine residue, Tyr 57, in histone H2A and is mediated by the unsuspected tyrosine kinase activity of casein kinase 2 (CK2). Mutation of Tyr 57 in H2A in yeast or inhibition of CK2 activity impairs transcriptional elongation in yeast as well as in mammalian cells. Genome-wide binding analysis reveals that CK2α, the catalytic subunit of CK2, binds across RNA-polymerase-II-transcribed coding genes and active enhancers. Mutation of Tyr 57 causes a loss of H2B mono-ubiquitination as well as H3K4me3 and H3K79me3, histone marks associated with active transcription. Mechanistically, both CK2 inhibition and the H2A(Y57F) mutation enhance H2B deubiquitination activity of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, suggesting a critical role of this phosphorylation in coordinating the activity of the SAGA complex during transcription. Together, these results identify a new component of regulation in transcriptional elongation based on CK2-dependent tyrosine phosphorylation of the globular domain of H2A.(doi:10.1038/nature13736

对应Nature杂志: 2014年12月11日Nature杂志精选

来源: Nature 浏览次数:61


RSS订阅 - 填写您的邮件地址,订阅我们的精彩内容: - 网站地图
网站联系电话:020-87540820 备案号:粤ICP备11050685号-8 增值电信业务经营许可证:粤B2-20120479
©2011-2015 生物帮 All rights reserved.