A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing.

TitleA basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing.
Publication TypeJournal Article
Year of Publication2020
AuthorsDao, HT, Dul, BE, Dann, GP, Liszczak, GP, Muir, TW
JournalNat Chem Biol
Volume16
Issue2
Pagination134-142
Date Published2020 02
ISSN1552-4469
KeywordsAdenosine Triphosphatases, Amino Acid Motifs, Binding Sites, Chromatin Assembly and Disassembly, Chromosomal Proteins, Non-Histone, Cysteine, DNA-Binding Proteins, Histones, Humans, Nucleosomes, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors
Abstract

Recent studies have implicated the nucleosome acidic patch in the activity of ATP-dependent chromatin remodeling machines. We used a photocrosslinking-based nucleosome profiling technology (photoscanning) to identify a conserved basic motif within the catalytic subunit of ISWI remodelers, SNF2h, which engages this nucleosomal epitope. This region of SNF2h is essential for chromatin remodeling activity in a reconstituted biochemical system and in cells. Our studies suggest that the basic motif in SNF2h plays a critical role in anchoring the remodeler to the nucleosomal surface. We also examine the functional consequences of several cancer-associated histone mutations that map to the nucleosome acidic patch. Kinetic studies using physiologically relevant heterotypic nucleosomal substrates ('Janus' nucleosomes) indicate that these cancer-associated mutations can disrupt regularly spaced chromatin structure by inducing ISWI-mediated unidirectional nucleosome sliding. These results indicate a potential mechanistic link between oncogenic histones and alterations to the chromatin landscape.

DOI10.1038/s41589-019-0413-4
Alternate JournalNat. Chem. Biol.
PubMed ID31819269
PubMed Central IDPMC6982587
Grant ListP01 CA196539 / CA / NCI NIH HHS / United States
R37 GM086868 / GM / NIGMS NIH HHS / United States