ISWI chromatin remodellers sense nucleosome modifications to determine substrate preference. Author Geoffrey Dann, Glen Liszczak, John Bagert, Manuel Müller, Uyen Nguyen, Felix Wojcik, Zachary Brown, Jeffrey Bos, Tatyana Panchenko, Rasmus Pihl, Samuel Pollock, Katharine Diehl, C David Allis, Tom Muir Publication Year 2017 Type Journal Article Abstract 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. Keywords Humans, Substrate Specificity, Transcription Factors, Models, Molecular, Adenosine Triphosphatases, Protein Subunits, Histones, Nucleosomes, Chromatin Assembly and Disassembly, DNA Barcoding, Taxonomic Journal Nature Volume 548 Issue 7669 Pages 607-611 Date Published 2017 Aug 31 ISSN Number 1476-4687 DOI 10.1038/nature23671 Alternate Journal Nature PMCID PMC5777669 PMID 28767641 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML