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Title: DNA Shape Dominates Sequence Affinity in Nucleosome Formation

Abstract

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.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1395068
DOE Contract Number:  
AC02-06CH11357
Resource Type:
Journal Article
Journal Name:
Physical Review Letters
Additional Journal Information:
Journal Volume: 113; Journal Issue: 16; Journal ID: ISSN 0031-9007
Publisher:
American Physical Society (APS)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Freeman, Gordon S., Lequieu, Joshua P., Hinckley, Daniel M., Whitmer, Jonathan K., and de Pablo, Juan J. DNA Shape Dominates Sequence Affinity in Nucleosome Formation. United States: N. p., 2014. Web. doi:10.1103/PhysRevLett.113.168101.
Freeman, Gordon S., Lequieu, Joshua P., Hinckley, Daniel M., Whitmer, Jonathan K., & de Pablo, Juan J. DNA Shape Dominates Sequence Affinity in Nucleosome Formation. United States. doi:10.1103/PhysRevLett.113.168101.
Freeman, Gordon S., Lequieu, Joshua P., Hinckley, Daniel M., Whitmer, Jonathan K., and de Pablo, Juan J. Wed . "DNA Shape Dominates Sequence Affinity in Nucleosome Formation". United States. doi:10.1103/PhysRevLett.113.168101.
@article{osti_1395068,
title = {DNA Shape Dominates Sequence Affinity in Nucleosome Formation},
author = {Freeman, Gordon S. and Lequieu, Joshua P. and Hinckley, Daniel M. and Whitmer, Jonathan K. and de Pablo, Juan J.},
abstractNote = {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.},
doi = {10.1103/PhysRevLett.113.168101},
journal = {Physical Review Letters},
issn = {0031-9007},
number = 16,
volume = 113,
place = {United States},
year = {2014},
month = {10}
}

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