Chromatin profiling reveals novel proteins associated with histone-marked genomic regions

Our understanding of the functions of DNA elements is limited by the paucity of information about the spectrum of proteins that occupy these genomic regions. Here we describe an approach to identify proteins associated with genomic regions whose chromatin is marked by specific modified histones, which we term chromatin profiling. We used chromatin immunoprecipitation followed by mass spectrometry (ChIP-MS) to identify proteins associated with genomic regions marked by histone H3K27Ac, H3K4me3, H3K79me2 and H3K36me3 in mouse embryonic stem (mES) cells. We identified 385 known and 224 novel candidate proteins associated with these histone-marked genomic segments and confirmed that several of the novel candidates are indeed associated with histone-marked segments of the genome. Future study of the novel candidates, many of which have been implicated in various diseases, should lead to an improved understanding of gene control and its dysregulation in disease.

目前学界对DNA元件功能的认知，因缺乏对结合于此类基因组区域的蛋白质谱系的相关信息而受到限制。在此我们介绍一种可识别与特定修饰组蛋白标记的染色质基因组区域相结合的蛋白质的方法，我们将该方法命名为染色质谱分析（chromatin profiling）。我们采用染色质免疫沉淀联合质谱（chromatin immunoprecipitation followed by mass spectrometry，ChIP-MS）技术，在小鼠胚胎干细胞（mouse embryonic stem cells，mES cells）中鉴定出结合于经组蛋白H3K27Ac、H3K4me3、H3K79me2及H3K36me3标记的基因组区域的蛋白质。本研究共鉴定得到385种已知蛋白与224种新型候选蛋白，并证实其中部分新型候选蛋白确实能够结合基因组的组蛋白标记区段。鉴于其中诸多新型候选蛋白已被证实与多种疾病相关，对其开展后续研究将有助于进一步深化对基因调控机制及其在疾病中失调机制的理解。