Long-distance combinatorial linkage between methylation and acetylation on histone H3N termini
Long-distance combinatorial linkage between methylation and acetylation on histone H3N termini
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DOI：
10.1073/pnas.0610993104
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发表时间：
2007-02-13
影响因子：
11.1
通讯作者：
Allis, C. David
中科院分区：
文献类型：
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作者：
Taverna, Sean D.;Ueberheide, Beatrix M.;Allis, C. David
组蛋白上的个体翻译后修饰(PTM)在某些生物学过程中具有广泛的作用，尤其是转录编程。最近的全基因组研究描述了共价修饰的模式，例如干细胞中特定靶基因的启动子上的H3甲基化和乙酰化，或者说是二价结构域，这表明在同一组蛋白上的PTM之间可能存在组合相互作用。然而，在基于抗体或传统的基于质谱学的分析中，检测远距离的PTM关联通常是有问题的。在这里，来自纤毛虫模型的组蛋白H3被分析为转录活性染色质的丰富来源。利用最近发展起来的一种质谱学方法，确定了单个长N末端H3片段(残基1-50)的组合修饰状态。获得了完整N末端的完整修饰状态，表明K4甲基化和H3乙酰化之间存在相关性。此外，在一个H3种上同时发现了K4和K27甲基化。这种方法也适用于其他组蛋白和较大的多肽，可能是理解PTM组合模式的作用的有价值的工具。
Individual posttranslational modifications (PTMs) on histones have well established roles in certain biological processes, notably transcriptional programming. Recent genomewide studies describe patterns of covalent modifications, such as H3 methylation and acetylation at promoters of specific target genes, or "bivalent domains," in stem cells, suggestive of a possible combinatorial interplay between PTMs on the same histone. However, detection of long-range PTM associations is often problematic in antibody-based or traditional mass spectrometric-based analyses. Here, histone H3 from a ciliate model was analyzed as an enriched source of transcriptionally active chromatin. Using a recently developed mass spectrometric approach, combinatorial modification states on single, long N-terminal H3 fragments (residues 1-50) were determined. The entire modification status of intact N termini was obtained and indicated correlations between K4 methylation and H3 acetylation. In addition, K4 and K27 methylation were identified concurrently on one H3 species. This methodology is applicable to other histones and larger polypepticles and will likely be a valuable tool in understanding the roles of combinatorial patterns of PTMs.