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      The biology and polymer physics underlying large‐scale chromosome organization

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          Abstract

          Chromosome large‐scale organization is a beautiful example of the interplay between physics and biology. DNA molecules are polymers and thus belong to the class of molecules for which physicists have developed models and formulated testable hypotheses to understand their arrangement and dynamic properties in solution, based on the principles of polymer physics. Biologists documented and discovered the biochemical basis for the structure, function and dynamic spatial organization of chromosomes in cells. The underlying principles of chromosome organization have recently been revealed in unprecedented detail using high‐resolution chromosome capture technology that can simultaneously detect chromosome contact sites throughout the genome. These independent lines of investigation have now converged on a model in which DNA loops, generated by the loop extrusion mechanism, are the basic organizational and functional units of the chromosome.

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          Most cited references116

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          Block copolymer thermodynamics: theory and experiment.

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            A genomic code for nucleosome positioning.

            Eukaryotic genomes are packaged into nucleosome particles that occlude the DNA from interacting with most DNA binding proteins. Nucleosomes have higher affinity for particular DNA sequences, reflecting the ability of the sequence to bend sharply, as required by the nucleosome structure. However, it is not known whether these sequence preferences have a significant influence on nucleosome position in vivo, and thus regulate the access of other proteins to DNA. Here we isolated nucleosome-bound sequences at high resolution from yeast and used these sequences in a new computational approach to construct and validate experimentally a nucleosome-DNA interaction model, and to predict the genome-wide organization of nucleosomes. Our results demonstrate that genomes encode an intrinsic nucleosome organization and that this intrinsic organization can explain approximately 50% of the in vivo nucleosome positions. This nucleosome positioning code may facilitate specific chromosome functions including transcription factor binding, transcription initiation, and even remodelling of the nucleosomes themselves.
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              Organization of the mitotic chromosome.

              Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.
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                Author and article information

                Contributors
                ssazer@bcm.edu
                schiessel@lorentz.leidenuniv.nl
                Journal
                Traffic
                Traffic
                10.1111/(ISSN)1600-0854
                TRA
                Traffic (Copenhagen, Denmark)
                John Wiley & Sons A/S (Former Munksgaard )
                1398-9219
                1600-0854
                03 December 2017
                February 2018
                : 19
                : 2 ( doiID: 10.1111/tra.2018.19.issue-2 )
                : 87-104
                Affiliations
                [ 1 ] Verna and Marrs McLean Department of Biochemistry and Molecular Biology Baylor College of Medicine Houston Texas
                [ 2 ] Institute Lorentz for Theoretical Physics Leiden University Leiden The Netherlands
                Author notes
                [*] [* ] Correspondence

                Shelley Sazer, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX.

                Email: ssazer@ 123456bcm.edu

                Helmut Schiessel, Instituut‐Lorentz for Theoretical Physics, Leiden University, Niels Bohrweg 2 Leiden 2333 CA, The Netherlands.

                Email: schiessel@ 123456lorentz.leidenuniv.nl

                Article
                TRA12539
                10.1111/tra.12539
                5846894
                29105235
                ec076d62-7d4f-4f69-a3d2-562017f861d8
                © 2017 The Authors. Traffic published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 31 July 2017
                : 31 October 2017
                : 31 October 2017
                Page count
                Figures: 9, Tables: 0, Pages: 18, Words: 17130
                Funding
                Funded by: National Science Foundation
                Award ID: NSF PHY11‐25915
                Funded by: Dutch Ministry of Education, Culture and Science
                Funded by: Kavli Institute for Theoretical Physics
                Categories
                Review
                Review
                Custom metadata
                2.0
                tra12539
                February 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:16.02.2018

                Sociology
                chromosome evolution,chromosome territory,chromosome tethering,cohesin,fractal globule,hi‐c,loop extrusion,polymer physics,smc,topologically associated domains

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