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      PML nuclear bodies and chromatin dynamics: catch me if you can!

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          Abstract

          Eukaryotic cells compartmentalize their internal milieu in order to achieve specific reactions in time and space. This organization in distinct compartments is essential to allow subcellular processing of regulatory signals and generate specific cellular responses. In the nucleus, genetic information is packaged in the form of chromatin, an organized and repeated nucleoprotein structure that is a source of epigenetic information. In addition, cells organize the distribution of macromolecules via various membrane-less nuclear organelles, which have gathered considerable attention in the last few years. The macromolecular multiprotein complexes known as Promyelocytic Leukemia Nuclear Bodies (PML NBs) are an archetype for nuclear membrane-less organelles. Chromatin interactions with nuclear bodies are important to regulate genome function. In this review, we will focus on the dynamic interplay between PML NBs and chromatin. We report how the structure and formation of PML NBs, which may involve phase separation mechanisms, might impact their functions in the regulation of chromatin dynamics. In particular, we will discuss how PML NBs participate in the chromatinization of viral genomes, as well as in the control of specific cellular chromatin assembly pathways which govern physiological mechanisms such as senescence or telomere maintenance.

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          Biomolecular condensates: organizers of cellular biochemistry

          In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge.
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            Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

            Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.
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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
                02 December 2020
                17 October 2020
                17 October 2020
                : 48
                : 21
                : 11890-11912
                Affiliations
                Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG) , team Chromatin Dynamics, Nuclear Domains, Virus F-69008, Lyon, France
                Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG) , team Chromatin Dynamics, Nuclear Domains, Virus F-69008, Lyon, France
                Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG) , team Chromatin Dynamics, Nuclear Domains, Virus F-69008, Lyon, France
                Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG) , team Chromatin Dynamics, Nuclear Domains, Virus F-69008, Lyon, France
                Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG) , team Chromatin Dynamics, Nuclear Domains, Virus F-69008, Lyon, France
                Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG) , team Chromatin Dynamics, Nuclear Domains, Virus F-69008, Lyon, France
                Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, LabEx DEVweCAN, Institut NeuroMyoGène (INMG) , team Chromatin Dynamics, Nuclear Domains, Virus F-69008, Lyon, France
                Author notes
                To whom correspondence should be addressed. Tel: +33 4 26 68 82 58; Fax: +33 4 26 68 82 92; Email: armelle.corpet@ 123456univ-lyon1.fr
                Correspondence may also be addressed to Patrick Lomonte. Tel: +33 4 26 68 82 57; Fax: +33 4 26 68 82 92; Email: patrick.lomonte@ 123456univ-lyon1.fr
                Author information
                http://orcid.org/0000-0002-2126-5783
                Article
                gkaa828
                10.1093/nar/gkaa828
                7708061
                33068409
                a1859140-7a5b-4f67-ae29-4a3105e21381
                © The Author(s) 2020. 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 Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 18 September 2020
                : 15 September 2020
                : 11 June 2020
                Page count
                Pages: 23
                Funding
                Funded by: Centre National de la Recherche Scientifique, DOI 10.13039/501100004794;
                Funded by: Institut National de la Santé et de la Recherche Médicale, DOI 10.13039/501100001677;
                Funded by: University Claude Bernard Lyon 1;
                Funded by: French National Agency for Research;
                Award ID: ANR-05-MIIM-008-01/02
                Award ID: ANR-13-BSV3-0001-01
                Award ID: ANR-18-CE15-0014-01
                Funded by: Comité départemental du Rhône de La Ligue contre le cancer;
                Funded by: FINOVI Foundation, DOI 10.13039/100008656;
                Award ID: 142690
                Categories
                AcademicSubjects/SCI00010
                Survey and Summary

                Genetics
                Genetics

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