The Gene-Silencing Protein MORC-1 Topologically Entraps DNA and Forms Multimeric Assemblies to Cause DNA Compaction

HyeongJun Kim; Linda Yen; Somsakul P Wongpalee; Jessica A Kirshner; Nicita Mehta; Yan Xue; Jonathan B Johnston; Alma L Burlingame; John K Kim; Joseph J Loparo; Steve E Jacobsen

doi:10.1016/j.molcel.2019.07.032

The Gene-Silencing Protein MORC-1 Topologically Entraps DNA and Forms Multimeric Assemblies to Cause DNA Compaction

Mol Cell. 2019 Aug 22;75(4):700-710.e6. doi: 10.1016/j.molcel.2019.07.032.

Authors

Affiliations

¹ 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 90095, USA.
² Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ 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.
⁴ Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
⁵ 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.
⁶ Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94158, USA.
⁷ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: joseph_loparo@hms.harvard.edu.
⁸ 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.

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.

Keywords: DNA compaction; DNA-binding protein; GHKL ATPases; MORC; genome organization.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caenorhabditis elegans / chemistry*
Caenorhabditis elegans / metabolism
Caenorhabditis elegans / ultrastructure
Caenorhabditis elegans Proteins / chemistry*
DNA, Helminth / chemistry*
DNA, Helminth / metabolism
Nuclear Proteins / chemistry*
Nucleic Acid Conformation*
Nucleosomes / chemistry*
Nucleosomes / metabolism
Nucleosomes / ultrastructure
Protein Multimerization*

Substances

Caenorhabditis elegans Proteins
DNA, Helminth
MORC-1 protein, C elegans
Nuclear Proteins
Nucleosomes

Abstract

Publication types

MeSH terms

Substances

Grants and funding