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      Chromatin fiber breaks into clutches under tension and crowding

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      Nucleic Acids Research
      Oxford University Press

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          Abstract

          The arrangement of nucleosomes inside chromatin is of extensive interest. While in vitro experiments have revealed the formation of 30 nm fibers, most in vivo studies have failed to confirm their presence in cell nuclei. To reconcile the diverging experimental findings, we characterized chromatin organization using a residue-level coarse-grained model. The computed force–extension curve matches well with measurements from single-molecule experiments. Notably, we found that a dodeca-nucleosome in the two-helix zigzag conformation breaks into structures with nucleosome clutches and a mix of trimers and tetramers under tension. Such unfolded configurations can also be stabilized through trans interactions with other chromatin chains. Our study suggests that unfolding from chromatin fibers could contribute to the irregularity of in vivo chromatin configurations. We further revealed that chromatin segments with fibril or clutch structures engaged in distinct binding modes and discussed the implications of these inter-chain interactions for a potential sol–gel phase transition.

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              Crystal structure of the nucleosome core particle at 2.8 A resolution.

              The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it. Both histone/histone and histone/DNA interactions depend on the histone fold domains and additional, well ordered structure elements extending from this motif. Histone amino-terminal tails pass over and between the gyres of the DNA superhelix to contact neighbouring particles. The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry.
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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                23 September 2022
                27 August 2022
                27 August 2022
                : 50
                : 17
                : 9738-9747
                Affiliations
                Department of Chemistry, Massachusetts Institute of Technology , Cambridge, MA, USA
                Department of Chemistry, Massachusetts Institute of Technology , Cambridge, MA, USA
                Department of Chemistry, Massachusetts Institute of Technology , Cambridge, MA, USA
                Author notes
                To whom correspondence should be addressed. Tel: +1 617 258 0848; Email: binz@ 123456mit.edu

                The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.

                Author information
                https://orcid.org/0000-0002-8569-5520
                https://orcid.org/0000-0002-9378-6174
                https://orcid.org/0000-0002-3685-7503
                Article
                gkac725
                10.1093/nar/gkac725
                9508854
                36029149
                1116846c-1576-487c-9f6f-a7050c494e32
                © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 August 2022
                : 08 July 2022
                : 17 January 2022
                Page count
                Pages: 10
                Funding
                Funded by: Directorate for Biological Sciences, DOI 10.13039/100000076;
                Award ID: MCB-2042362
                Funded by: National Institute of General Medical Sciences, DOI 10.13039/100000057;
                Award ID: R35GM133580
                Categories
                AcademicSubjects/SCI00010
                Gene regulation, Chromatin and Epigenetics

                Genetics
                Genetics

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