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In silico evidence for sequence-dependent nucleosome sliding
Journal article

In silico evidence for sequence-dependent nucleosome sliding

Joshua Lequieu, David C Schwartz and Juan J de Pablo
Proceedings of the National Academy of Sciences - PNAS, v 114(44), pp E9197-E9205
31 Oct 2017
PMID: 29078285
url
https://doi.org/10.1073/pnas.1705685114View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Restricted

Abstract

Chromatin - genetics Chromatin Assembly and Disassembly - genetics Computer Simulation DNA - genetics Gene Silencing - physiology Genome - genetics Histones - genetics Models, Molecular Nucleosomes - genetics
Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. These processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nucleosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nucleosome repositioning. The mechanism of nucleosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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