Ji Xiong, Dadon Daniel B, Abraham Brian J, Lee Tong Ihn, Jaenisch Rudolf, Bradner James E, Young Richard A
Whitehead Institute for Biomedical Research, Cambridge, MA 02142;
Whitehead Institute for Biomedical Research, Cambridge, MA 02142; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139;
Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3841-6. doi: 10.1073/pnas.1502971112. Epub 2015 Mar 9.
More than a thousand proteins are thought to contribute to mammalian chromatin and its regulation, but our understanding of the genomic occupancy and function of most of these proteins is limited. Here we describe an approach, which we call "chromatin proteomic profiling," to identify proteins associated with genomic regions marked by specifically modified histones. We used ChIP-MS to identify proteins associated with genomic regions marked by histones modified at specific lysine residues, including H3K27ac, H3K4me3, H3K79me2, H3K36me3, H3K9me3, and H4K20me3, in ES cells. We identified 332 known and 114 novel proteins associated with these histone-marked genomic segments. Many of the novel candidates have been implicated in various diseases, and their chromatin association may provide clues to disease mechanisms. More than 100 histone modifications have been described, so similar chromatin proteomic profiling studies should prove to be valuable for identifying many additional chromatin-associated proteins in a broad spectrum of cell types.
据认为，超过一千种蛋白质参与哺乳动物染色质及其调控，但我们对其中大多数蛋白质的基因组占据情况和功能的了解有限。在此，我们描述了一种方法，我们称之为“染色质蛋白质组分析”，用于鉴定与由特定修饰组蛋白标记的基因组区域相关的蛋白质。我们使用染色质免疫沉淀-质谱联用（ChIP-MS）来鉴定与胚胎干细胞中在特定赖氨酸残基处修饰的组蛋白所标记的基因组区域相关的蛋白质，这些赖氨酸残基包括H3K27ac、H3K4me3、H3K79me2、H3K36me3、H3K9me3和H4K20me3。我们鉴定出与这些组蛋白标记的基因组片段相关的332种已知蛋白质和114种新蛋白质。许多新的候选蛋白质与各种疾病有关，它们与染色质的关联可能为疾病机制提供线索。已经描述了超过100种组蛋白修饰，因此类似的染色质蛋白质组分析研究对于在广泛的细胞类型中鉴定许多其他染色质相关蛋白质应该是有价值的。
