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DNA shape dominates sequence affinity in nucleosome formation
Journal article   Open access   Peer reviewed

DNA shape dominates sequence affinity in nucleosome formation

Gordon S Freeman, Joshua P Lequieu, Daniel M Hinckley, Jonathan K Whitmer and Juan J de Pablo
Physical review letters, v 113(16), pp 168101-168101
17 Oct 2014
PMID: 25361282
url
https://doi.org/10.1103/PhysRevLett.113.168101View
Published, Version of Record (VoR) Open

Abstract

DNA - chemistry DNA - genetics DNA - metabolism Eukaryota - chemistry Eukaryota - genetics Eukaryota - metabolism Histones - chemistry Histones - genetics Histones - metabolism Models, Chemical Models, Genetic Models, Molecular Nucleic Acid Conformation Nucleosomes - chemistry Nucleosomes - genetics Nucleosomes - metabolism Static Electricity Structure-Activity Relationship
Nucleosomes provide the basic unit of compaction in eukaryotic genomes, and the mechanisms that dictate their position at specific locations along a DNA sequence are of central importance to genetics. In this Letter, we employ molecular models of DNA and proteins to elucidate various aspects of nucleosome positioning. In particular, we show how DNA's histone affinity is encoded in its sequence-dependent shape, including subtle deviations from the ideal straight B-DNA form and local variations of minor groove width. By relying on high-precision simulations of the free energy of nucleosome complexes, we also demonstrate that, depending on DNA's intrinsic curvature, histone binding can be dominated by bending interactions or electrostatic interactions. More generally, the results presented here explain how sequence, manifested as the shape of the DNA molecule, dominates molecular recognition in the problem of nucleosome positioning.

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Collaboration types
Domestic collaboration
Web of Science research areas
Physics, Multidisciplinary
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