Decoding chromatin states by proteomic profiling of nucleosome readers

• 成果类型: Article
• 署名作者: Lukauskas, Saulius; Tvardovskiy, Andrey; Nguyen, Nhuong V.; Stadler, Mara; Faull, Peter; Ravnsborg, Tina; Aygenli, Bihter Ozdemir; Dornauer, Scarlett; Flynn, Helen; Lindeboom, Rik G. H.; Barth, Teresa K.; Brockers, Kevin; Hauck, Stefanie M.; Vermeulen, Michiel; Snijders, Ambrosius P.; Mueller, Christian L.; DiMaggio, Peter A.; Jensen, Ole N.; Schneider, Robert; Bartke, Till
• 署名单位: Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Imperial College London; Imperial College London; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; University of Munich; Francis Crick Institute; University of Southern Denmark; University of Southern Denmark; Radboud University Nijmegen; Netherlands Cancer Institute; Helmholtz Association; Helmholtz-Center Munich - German Research Center for Environmental Health; Simons Foundation; Flatiron Institute; University of Munich; German Center for Diabetes Research (DZD); Northwestern University; University of Munich
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4742
• DOI: 10.1038/s41586-024-07141-5
• 发表日期: 2024-03-21
• 关键词: combinatorial modification; histone methylation; human interactome; dna; identification; encyclopedia; proteins; binding; LINKS; h3

摘要

DNA and histone modifications combine into characteristic patterns that demarcate functional regions of the genome1,2. While many 'readers' of individual modifications have been described3-5, how chromatin states comprising composite modification signatures, histone variants and internucleosomal linker DNA are interpreted is a major open question. Here we use a multidimensional proteomics strategy to systematically examine the interaction of around 2,000 nuclear proteins with over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states. By deconvoluting complex nucleosome-binding profiles into networks of co-regulated proteins and distinct nucleosomal features driving protein recruitment or exclusion, we show comprehensively how chromatin states are decoded by chromatin readers. We find highly distinctive binding responses to different features, many factors that recognize multiple features, and that nucleosomal modifications and linker DNA operate largely independently in regulating protein binding to chromatin. Our online resource, the Modification Atlas of Regulation by Chromatin States (MARCS), provides in-depth analysis tools to engage with our results and advance the discovery of fundamental principles of genome regulation by chromatin states. A multidimensional proteomics analysis of the interactions between around 2,000 nuclear proteins and over 80 modified dinucleosomes representing promoter, enhancer and heterochromatin states provides insights into how chromatin states are decoded by chromatin readers.