Article, 2024
Decoding chromatin states by proteomic profiling of nucleosome readers
Nature,
ISSN
0028-0836,
1476-4687,
Volume 627,
8004,
Pages 671-679,
10.1038/s41586-024-07141-5
Contributors
Lukauskas, Saulius
0000-0001-9781-2707
[1]
[2]
[3]
Tvardovskiy, Andrey A
0000-0003-3252-280X
[1]
Nguyen, Nhuong V
0000-0003-4152-5113
[2]
[3]
Stadler, Mara
0000-0002-1241-031X
[1]
[4]
Faull, Peter A
0000-0001-8491-8086
[3]
[5]
[6]
Ravnsborg, Tina
0000-0002-6376-621X
[7]
Özdemir Aygenli, Bihter
[1]
Dornauer, Scarlett
[1]
Flynn, Helen R
0000-0001-7002-9130
[6]
Lindeboom, Rik G H
0000-0002-3660-504X
[8]
[9]
Barth, Teresa K
[1]
[4]
Brockers, Kevin
[1]
Hauck, Stefanie M
0000-0002-1630-6827
[1]
Vermeulen, M Vermeulen Prof M
0000-0003-0836-6894
[8]
[9]
Snijders, Ambrosius P L
0000-0002-5416-8592
[6]
Müller, Christian L
0000-0002-3821-7083
[1]
[4]
[10]
Dimaggio, Peter A
0000-0003-1996-0813
[2]
Jensen, Ole Noerregaard
0000-0003-1862-8528
[7]
Schneider, Robert J
0000-0001-5807-5564
[1]
[4]
[11]
Bartke, Till
(Corresponding author)
[1]
[2]
[3]
Affiliations
- [1]
Helmholtz Zentrum München
[NORA names:
Germany; Europe, EU; OECD];
- [2]
Imperial College London
[NORA names:
United Kingdom; Europe, Non-EU; OECD];
- [3]
Medical Research Council
[NORA names:
United Kingdom; Europe, Non-EU; OECD];
- [4]
Ludwig-Maximilians-Universität München
[NORA names:
Germany; Europe, EU; OECD];
- [5]
Northwestern University
[NORA names:
United States; America, North; OECD];
(... more)
- [6]
The Francis Crick Institute
[NORA names:
United Kingdom; Europe, Non-EU; OECD];
- [7]
University of Southern Denmark
[NORA names:
SDU University of Southern Denmark;
University; Denmark; Europe, EU; Nordic; OECD];
- [8]
Antoni van Leeuwenhoek Hospital
[NORA names:
Netherlands; Europe, EU; OECD];
- [9]
Radboud University Nijmegen
[NORA names:
Netherlands; Europe, EU; OECD];
- [10]
Flatiron Institute
[NORA names:
United States; America, North; OECD];
- [11]
German Center for Diabetes Research
[NORA names:
Germany; Europe, EU; OECD]
(less)
Abstract
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.
Keywords
DNA,
MARC,
analysis,
analysis tools,
binding,
binding to chromatin,
characteristic pattern,
chromatin,
chromatin readers,
chromatin state,
co-regulator proteins,
described3,
different features,
dinucleosomes,
discovery,
enhancement,
exclusion,
factors,
features,
functional regions,
genome,
genome regulation,
genome1,2,
heterochromatin,
heterochromatin state,
histone,
histone modifications,
histone variants,
individual modifications,
interaction,
internucleosomal linker DNA,
linker,
linker DNA,
modification,
modification signatures,
multiple features,
network,
nuclear proteins,
nucleosome features,
nucleosome modification,
patterns,
profile,
promoter,
protein,
protein binding to chromatin,
protein recruitment,
proteomic profiling,
proteomic strategy,
readers,
recruitment,
region,
regulation,
resources,
response to different features,
results,
signature,
state,
strategies,
tools,
variants
Funders
Data Provider: Digital Science