Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes.

TitleChromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes.
Publication TypeJournal Article
Year of Publication2021
AuthorsMashtalir, N, Dao, HT, Sankar, A, Liu, H, Corin, AJ, Bagert, JD, Ge, EJ, D'Avino, AR, Filipovski, M, Michel, BC, Dann, GP, Muir, TW, Kadoch, C
JournalScience
Volume373
Issue6552
Pagination306-315
Date Published2021 07 16
ISSN1095-9203
KeywordsAdenosine Triphosphatases, Adenosine Triphosphate, Chromatin, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Histone Code, Histones, Humans, Models, Molecular, Multiprotein Complexes, Mutation, Nucleosomes, Protein Binding, Protein Domains, Protein Subunits, Transcription Factors
Abstract

<p>Mammalian SWI/SNF (mSWI/SNF) adenosine triphosphate-dependent chromatin remodelers modulate genomic architecture and gene expression and are frequently mutated in disease. However, the specific chromatin features that govern their nucleosome binding and remodeling activities remain unknown. We subjected endogenously purified mSWI/SNF complexes and their constituent assembly modules to a diverse library of DNA-barcoded mononucleosomes, performing more than 25,000 binding and remodeling measurements. Here, we define histone modification-, variant-, and mutation-specific effects, alone and in combination, on mSWI/SNF activities and chromatin interactions. Further, we identify the combinatorial contributions of complex module components, reader domains, and nucleosome engagement properties to the localization of complexes to selectively permissive chromatin states. These findings uncover principles that shape the genomic binding and activity of a major chromatin remodeler complex family.</p>

DOI10.1126/science.abf8705
Alternate JournalScience
PubMed ID34437148
PubMed Central IDPMC8390793
Grant ListK99 CA237855 / CA / NCI NIH HHS / United States
P01 CA196539 / CA / NCI NIH HHS / United States
DP2 CA195762 / CA / NCI NIH HHS / United States
R37 GM086868 / GM / NIGMS NIH HHS / United States
F32 GM123659 / GM / NIGMS NIH HHS / United States