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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)134-142
Number of pages9
JournalNature Chemical Biology
Volume16
Issue number2
DOIs
StatePublished - Feb 1 2020

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Nucleosomes
Chromatin Assembly and Disassembly
Histones
Chromatin
Mutation
Epitopes
Catalytic Domain
Neoplasms
Adenosine Triphosphate
Technology

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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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.",
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A basic motif anchoring ISWI to nucleosome acidic patch regulates nucleosome spacing. / Muir, Tom W.

In: Nature Chemical Biology, Vol. 16, No. 2, 01.02.2020, p. 134-142.

Research output: Contribution to journalArticle

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