title: Why Do Nucleosomes Unwrap Asymmetrically?
abstract: Nucleosomes, DNA spools with a protein core, engage about three-quarters of eukaryotic DNA and play a critical role in chromosomal processes, ranging from gene regulation, recombination, and replication to chromosome condensation. For more than a decade, micromanipulation experiments where nucleosomes are put under tension, as well as the theoretical interpretations of these experiments, have deepened our understanding of the stability and dynamics of nucleosomes. Here we give a theoretical explanation for a surprising new experimental finding: nucleosomes wrapped onto the 601 positioning sequence (the sequence used in most laboratories) respond highly asymmetrically to external forces by always unwrapping from the same end. Using a computational nucleosome model, we show that this asymmetry can be explained by differences in the DNA mechanics of two very short stretches on the wrapped DNA portion. Our finding suggests that the physical properties of nucleosomes, here the response to forces, can be tuned locally by the choice of the underlying base-pair sequence. This leads to a new view of nucleosomes: a physically highly varied set of DNA-protein complexes whose properties can be tuned on evolutionary time scales to their specific function in the genomic context.
authors.affiliation: Institute Lorentz for Theoretical Physics, Leiden University , Niels Bohrweg 2, 2333 CA Leiden, The Netherlands.
authors.forename: Lennart
authors.initials: L
authors.lastname: de Bruin
authors.affiliation: Institute Lorentz for Theoretical Physics, Leiden University , Niels Bohrweg 2, 2333 CA Leiden, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Tompitak
authors.affiliation: Institute Lorentz for Theoretical Physics, Leiden University , Niels Bohrweg 2, 2333 CA Leiden, The Netherlands.|Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology , Lorentzweg 1, 2628 CJ Delft, The Netherlands.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Eslami-Mossallam
authors.affiliation: Institute Lorentz for Theoretical Physics, Leiden University , Niels Bohrweg 2, 2333 CA Leiden, The Netherlands.
authors.forename: Helmut
authors.initials: H
authors.lastname: Schiessel
mesh_terms: D000465:Algorithms; D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D006657:Histones; D009707:Nucleosomes; D009711:Nucleotides; D004247:DNA