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The Gene-Silencing Protein MORC-1 Topologically Entraps DNA and Forms Multimeric Assemblies to Cause DNA Compaction.
Kim, HyeongJun; Yen, Linda; Wongpalee, Somsakul P; Kirshner, Jessica A; Mehta, Nicita; Xue, Yan; Johnston, Jonathan B; Burlingame, Alma L; Kim, John K; Loparo, Joseph J; Jacobsen, Steve E.
Afiliação
  • Kim H; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Physics and Astronomy, University of Texas Rio Grande Valley, Edinburg, TX 78539, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 9
  • Yen L; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wongpalee SP; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
  • Kirshner JA; Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
  • Mehta N; Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
  • Xue Y; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Johnston JB; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Burlingame AL; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Kim JK; Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
  • Loparo JJ; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: joseph_loparo@hms.harvard.edu.
  • Jacobsen SE; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: jacobsen@ucla.edu.
Mol Cell ; 75(4): 700-710.e6, 2019 08 22.
Article em En | MEDLINE | ID: mdl-31442422
ABSTRACT
Microrchidia (MORC) ATPases are critical for gene silencing and chromatin compaction in multiple eukaryotic systems, but the mechanisms by which MORC proteins act are poorly understood. Here, we apply a series of biochemical, single-molecule, and cell-based imaging approaches to better understand the function of the Caenorhabditis elegans MORC-1 protein. We find that MORC-1 binds to DNA in a length-dependent but sequence non-specific manner and compacts DNA by forming DNA loops. MORC-1 molecules diffuse along DNA but become static as they grow into foci that are topologically entrapped on DNA. Consistent with the observed MORC-1 multimeric assemblies, MORC-1 forms nuclear puncta in cells and can also form phase-separated droplets in vitro. We also demonstrate that MORC-1 compacts nucleosome templates. These results suggest that MORCs affect genome structure and gene silencing by forming multimeric assemblages to topologically entrap and progressively loop and compact chromatin.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Nucleossomos / Caenorhabditis elegans / DNA de Helmintos / Proteínas de Caenorhabditis elegans / Multimerização Proteica / Conformação de Ácido Nucleico Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Nucleossomos / Caenorhabditis elegans / DNA de Helmintos / Proteínas de Caenorhabditis elegans / Multimerização Proteica / Conformação de Ácido Nucleico Idioma: En Ano de publicação: 2019 Tipo de documento: Article