Quantitative Interaction Proteomics and Genome-wide Profiling of Epigenetic Histone Marks and Their Readers
Quantitative Interaction Proteomics and Genome-wide Profiling of Epigenetic Histone Marks and Their Readers
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DOI：
10.1016/j.cell.2010.08.020
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发表时间：
2010-09-17
期刊：
影响因子：
64.5
通讯作者：
Mann, Matthias
中科院分区：
文献类型：
--
作者：
Vermeulen, Michiel;Eberl, H. Christian;Mann, Matthias
组蛋白上的三甲基赖氨酸 (me3) 修饰是最稳定的表观遗传标记，它们控制染色质介导的基因表达调节。在这里，我们通过高精度定量质谱法确定结合这些标记的蛋白质。这些染色质“阅读器”通过全长 BAC-GFP 标记蛋白的相互作用蛋白质组学分配给复合物。ChIP-Seq 分析鉴定了它们的基因组结合位点，揭示了功能特性。主要发现之一是，人类 SAGA 复合物通过 Sgf29 C 末端的双 Tudor 结构域与 H3K4me3 结合，并且 PWWP 结构域被鉴定为假定的 H3K36me3 结合基序。包括 LRWD1 在内的复合物与三个最显着的转录抑制赖氨酸甲基化位点结合，我们的数据揭示了染色质标记与其相关蛋白质复合物之间高度适应的相互作用。
Trimethyl-lysine (me3) modifications on histones are the most stable epigenetic marks and they control chromatin-mediated regulation of gene expression. Here, we determine proteins that bind these marks by high-accuracy, quantitative mass spectrometry. These chromatin "readers'' are assigned to complexes by interaction proteomics of full-length BAC-GFP-tagged proteins. ChIP-Seq profiling identifies their genomic binding sites, revealing functional properties. Among the main findings, the human SAGA complex binds to H3K4me3 via a double Tudor-domain in the C terminus of Sgf29, and the PWWP domain is identified as a putative H3K36me3 binding motif. The ORC complex, including LRWD1, binds to the three most prominent transcriptional repressive lysine methylation sites. Our data reveal a highly adapted interplay between chromatin marks and their associated protein complexes. Reading specific trimethyl-lysine sites by specialized complexes appears to be a widespread mechanism to mediate gene expression.