Histone peptide microarray screen of chromo and Tudor domains defines new histone lysine methylation interactions.
Histone peptide microarray screen of chromo and Tudor domains defines new histone lysine methylation interactions.
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DOI：
10.1186/s13072-017-0117-5
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发表时间：
2017
影响因子：
3.9
通讯作者：
Strahl BD
中科院分区：
文献类型：
--
作者：
Shanle EK;Shinsky SA;Bridgers JB;Bae N;Sagum C;Krajewski K;Rothbart SB;Bedford MT;Strahl BD
组蛋白翻译后修饰 (PTM) 的功能部分是通过招募含有专门“阅读器”结构域的效应蛋白来调节染色质结构和功能。尽管努力阐明读者域与 PTM 的相互作用，但邻近 PTM 的影响和许多读者域的目标特异性仍不清楚。本研究的目的是使用高通量组蛋白肽微阵列平台来询问来自 chromo 和 Tudor 结构域家族的 83 个已知和推定的组蛋白读取结构域，以识别它们的相互作用并表征相邻 PTM 对这些相互作用的影响。 通过肽微阵列，筛选的近四分之一的染色体和 Tudor 结构域显示出与组蛋白 PTM 的相互作用，揭示了已知的和几种新的甲基赖氨酸相互作用。具体来说，我们发现识别 H3K9me 的 CBX/HP1 染色质结构域也识别 H3K23me2/3——一种人们知之甚少的组蛋白 PTM。我们还观察到，除了与 H3K4me3 相互作用之外，Spindlin 家族的 Tudor 结构域还识别 H4K20me3——一种以前未表征的相互作用。几个 Tudor 域也显示出与 H3K4me 的新颖相互作用。这些结果为表观遗传学和染色质界研究许多人类染色体和都铎结构域的相互作用提供了重要资源。它们还为进一步研究所发现的新颖相互作用的功能意义提供了基础。本文的在线版本 (doi:10.1186/s13072-017-0117-5) 包含补充材料，可供授权用户使用。
Histone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized “reader” domains. Despite efforts to elucidate reader domain–PTM interactions, the influence of neighboring PTMs and the target specificity of many reader domains is still unclear. The aim of this study was to use a high-throughput histone peptide microarray platform to interrogate 83 known and putative histone reader domains from the chromo and Tudor domain families to identify their interactions and characterize the influence of neighboring PTMs on these interactions. Nearly a quarter of the chromo and Tudor domains screened showed interactions with histone PTMs by peptide microarray, revealing known and several novel methyllysine interactions. Specifically, we found that the CBX/HP1 chromodomains that recognize H3K9me also recognize H3K23me2/3—a poorly understood histone PTM. We also observed that, in addition to their interaction with H3K4me3, Tudor domains of the Spindlin family also recognized H4K20me3—a previously uncharacterized interaction. Several Tudor domains also showed novel interactions with H3K4me as well. These results provide an important resource for the epigenetics and chromatin community on the interactions of many human chromo and Tudor domains. They also provide the basis for additional studies into the functional significance of the novel interactions that were discovered. The online version of this article (doi:10.1186/s13072-017-0117-5) contains supplementary material, which is available to authorized users.