ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference.

TitleISWI chromatin remodellers sense nucleosome modifications to determine substrate preference.
Publication TypeJournal Article
Year of Publication2017
AuthorsDann, GP, Liszczak, GP, Bagert, JD, Müller, MM, Nguyen, UTT, Wojcik, F, Brown, ZZ, Bos, J, Panchenko, T, Pihl, R, Pollock, SB, Diehl, KL, C Allis, D, Muir, TW
JournalNature
Volume548
Issue7669
Pagination607-611
Date Published2017 08 31
ISSN1476-4687
KeywordsAdenosine Triphosphatases, Chromatin Assembly and Disassembly, DNA Barcoding, Taxonomic, Histones, Humans, Models, Molecular, Nucleosomes, Protein Subunits, Substrate Specificity, Transcription Factors
Abstract

<p>ATP-dependent chromatin remodellers regulate access to genetic information by controlling nucleosome positions in vivo. However, the mechanism by which remodellers discriminate between different nucleosome substrates is poorly understood. Many chromatin remodelling proteins possess conserved protein domains that interact with nucleosomal features. Here we used a quantitative high-throughput approach, based on the use of a DNA-barcoded mononucleosome library, to profile the biochemical activity of human ISWI family remodellers in response to a diverse set of nucleosome modifications. We show that accessory (non-ATPase) subunits of ISWI remodellers can distinguish between differentially modified nucleosomes, directing remodelling activity towards specific nucleosome substrates according to their modification state. Unexpectedly, we show that the nucleosome acidic patch is necessary for maximum activity of all ISWI remodellers evaluated. This dependence also extends to CHD and SWI/SNF family remodellers, suggesting that the acidic patch may be generally required for chromatin remodelling. Critically, remodelling activity can be regulated by modifications neighbouring the acidic patch, signifying that it may act as a tunable interaction hotspot for ATP-dependent chromatin remodellers and, by extension, many other chromatin effectors that engage this region of the nucleosome surface.</p>

DOI10.1038/nature23671
Alternate JournalNature
PubMed ID28767641
PubMed Central IDPMC5777669
Grant ListP01 CA196539 / CA / NCI NIH HHS / United States
R01 CA204639 / CA / NCI NIH HHS / United States
R01 GM086868 / GM / NIGMS NIH HHS / United States
GM112365 / NH / NIH HHS / United States
T32 GM007388 / GM / NIGMS NIH HHS / United States
F32 CA206418 / CA / NCI NIH HHS / United States
R37 GM086868 / GM / NIGMS NIH HHS / United States
F32 GM112365 / GM / NIGMS NIH HHS / United States
R01 GM107047 / GM / NIGMS NIH HHS / United States