Title | A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Dao, HT, Dul, BE, Dann, GP, Liszczak, GP, Muir, TW |
Journal | Nat Chem Biol |
Volume | 16 |
Issue | 2 |
Pagination | 134-142 |
Date Published | 2020 02 |
ISSN | 1552-4469 |
Keywords | Adenosine 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 | <p>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.</p> |
DOI | 10.1038/s41589-019-0413-4 |
Alternate Journal | Nat Chem Biol |
PubMed ID | 31819269 |
PubMed Central ID | PMC6982587 |
Grant List | P01 CA196539 / CA / NCI NIH HHS / United States R37 GM086868 / GM / NIGMS NIH HHS / United States |