Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing

The eukaryotic microrchidia (MORC) protein family are DNA gyrase, Hsp90, histidine kinase, MutL (GHKL)-type ATPases involved in gene expression regulation and chromatin compaction. The molecular mechanisms underlying these activities are incompletely understood. Here, we studied the full-length human MORC2 protein biochemically. We identified a DNA binding site in the C-terminus of the protein, and we observe that this region can be phosphorylated in cells. DNA binding by MORC2 reduces its ATPase activity and MORC2 can entrap multiple DNA substrates between its N-terminal GHKL and C-terminal coiled coil 3 dimerization domains. Finally, we observe that the MORC2 C-terminal DNA binding region is required for gene silencing in cells. Together, our data provide a model to understand how MORC2 engages with DNA substrates to mediate gene silencing.

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Publication Details

Journal
Nucleic Acids Research
Published
2024-12-12
DOI
https://doi.org/10.1093/nar/gkae1273
Citations
8
Primary Topic
Heat shock proteins research
Type
article
Field-Weighted Citation Impact
1.87

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article

Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing

Nikole L. Fendler, Fabian Schulte, Seychelle M. Vos, Dan Lü et al.
8 citations
Nucleic Acids Research
Heat shock proteins research
1.87
article

Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing

Nikole L. Fendler, Fabian Schulte, Seychelle M. Vos, Dan Lü, Jimmy Ly, Luisa M. Welp, Henning Urlaub
article en
8 citations

Abstract

The eukaryotic microrchidia (MORC) protein family are DNA gyrase, Hsp90, histidine kinase, MutL (GHKL)-type ATPases involved in gene expression regulation and chromatin compaction. The molecular mechanisms underlying these activities are incompletely understood. Here, we studied the full-length human MORC2 protein biochemically. We identified a DNA binding site in the C-terminus of the protein, and we observe that this region can be phosphorylated in cells. DNA binding by MORC2 reduces its ATPase activity and MORC2 can entrap multiple DNA substrates between its N-terminal GHKL and C-terminal coiled coil 3 dimerization domains. Finally, we observe that the MORC2 C-terminal DNA binding region is required for gene silencing in cells. Together, our data provide a model to understand how MORC2 engages with DNA substrates to mediate gene silencing.

Nucleic Acids ResearchVol. 53(4)
Howard Hughes Medical Institute (US), Harvard University (US), Bioanalytica (Switzerland) (CH), Universitätsmedizin Göttingen (DE), Center for Systems Biology (US), Whitehead Institute for Biomedical Research (US), Massachusetts Institute of Technology (US), University of Göttingen (DE)
National Science Foundation, Howard Hughes Medical Institute, Richard and Susan Smith Family Foundation, Alex's Lemonade Stand Foundation for Childhood Cancer, Deutsche Forschungsgemeinschaft, Natural Sciences and Engineering Research Council of Canada, National Institute of General Medical Sciences
Openalex Percentile: Top 14%
Heat shock proteins research
1.87
DOIOpen Access PDFOpenAlex
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