Regulation of chromatin folding by conformational variations of nucleosome linker DNA

Jenna M. Buckwalter, Davood Norouzi, Anna Harutyunyan, Victor B. Zhurkin, Sergei A. Grigoryev

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Linker DNA conformational variability has been proposed to direct nucleosome array folding into more or less compact chromatin fibers but direct experimental evidence for such models are lacking. Here, we tested this hypothesis by designing nucleosome arrays with A-tracts at specific locations in the nucleosome linkers to induce inward (AT-IN) and outward (AT-OUT) bending of the linker DNA. Using electron microscopy and analytical centrifugation techniques, we observed spontaneous folding of AT-IN nucleosome arrays into highly compact structures, comparable to those induced by linker histone H1. In contrast, AT-OUT nucleosome arrays formed less compact structures with decreased nucleosome interactions similar to wild-type nucleosome arrays. Adding linker histone H1 further increased compaction of the A-tract arrays while maintaining structural differences between them. Furthermore, restriction nuclease digestion revealed a strongly reduced accessibility of nucleosome linkers in the compact AT-IN arrays. Electron microscopy analysis and 3D computational Monte Carlo simulations are consistent with a profound zigzag linker DNA configuration and closer nucleosome proximity in the AT-IN arrays due to inward linker DNA bending. We propose that the evolutionary preferred positioning of A-tracts in DNA linkersmay control chromatin higher-order folding and thus influence cellular processes such as gene expression, transcription and DNA repair.

Original languageEnglish (US)
Pages (from-to)9372-9387
Number of pages16
JournalNucleic acids research
Volume45
Issue number16
DOIs
StatePublished - Sep 19 2017

All Science Journal Classification (ASJC) codes

  • Genetics

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