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.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Freeman
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Lequieu
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Hinckley
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA and Institute for Molecular Engineering, University of Chicago, Chicago, Illinois 60637, USA and Materials Science Division, Argonne National Laboratory, Argonne, Illinois 60439, USA.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Whitmer
authors.affiliation: Institute for Molecular Engineering, University of Chicago, Chicago, Illinois 60637, USA and Materials Science Division, Argonne National Laboratory, Argonne, Illinois 60439, USA.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: de Pablo
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D056890:Eukaryota / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D006657:Histones; D009707:Nucleosomes; D004247:DNA