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Lukauskas, S. ; Tvardovskiy, A. ; Nguyen, N.V.* ; Stadler, M. ; Faull, P.* ; Ravnsborg, T.* ; Özdemir Aygenli, B. ; Dornauer, S. ; Flynn, H.* ; Lindeboom, R.G.H.* ; Barth, T.K. ; Brockers, K. ; Hauck, S.M. ; Vermeulen, M.* ; Snijders, A.P.* ; Müller, C.L. ; DiMaggio, P.A.* ; Jensen, O.N.* ; Schneider, R. ; Bartke, T.

Decoding chromatin states by proteomic profiling of nucleosome readers.

Nature 627, 671-679 (2024)
DOI PMC
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Combinatorial Modification; Histone Methylation; Human Interactome; Dna; Identification; Encyclopedia; Proteins; Binding; Links; H3
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Journal Nature
Quellenangaben Volume: 627, Issue: 8004, Pages: 671-679 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Functional Epigenetics (IFE)
Institute of Computational Biology (ICB)
CF Metabolomics & Proteomics (CF-MPC)
Grants BBSRC DTP PhD studentship award
Deutsche Forschungsgemeinschaft (DFG project)
Helmholtz Gesellschaft
European Research Council
Helmholtz Gesellschaft - UK Medical Research Council
Deutsche Forschungsgemeinschaft (DFG)
Helmholtz Gesellschaft through a Munich School for Data Science
Francis Crick Institute
Cancer Research UK
UK Medical Research Council
Wellcome Trust
VILLUM Center for Bioanalytical Sciences (VILLUM Foundation)
INTEGRA (Novo Nordisk Foundation)
Dutch Cancer Society