Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing
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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.
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- Authors
- Fendler, N. L., Ly, J., Welp, L., Lu, D., Schulte, F., Urlaub, H., & Vos, S. M.
- Affiliations
- Massachusetts Institute of Technology (US)
- Whitehead Institute for Biomedical Research (US)
- Universitätsmedizin Göttingen (DE)
- Department of Systems Biology, Harvard Medical School , 210 Longwood Avenue , Boston , MA 02115,
- Howard Hughes Medical Institute (US)
- Corresponding author
- Vos, Seychelle M
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2024-12-31
- Volume
- 53
- Issue
- 4
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC11879086
- OpenAlex
- W4405951774
- Cited by
- 12
- References
- 3
- Citations by year
- 2026: 5 · 2025: 7
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (SFB1565)
- National Science Foundation
- National Institute of General Medical Sciences (R35GM126930, DP2-GM146254)
- Howard Hughes Medical Institute
- Smith Family Foundation
- Alex’s Lemonade Stand Foundation for Childhood Cancer
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- MORC2, DNA binding sites, gene silencing, protein phosphorylation, ATPase activity, coiled-coil dimerization, chromatin condensation, gene expression regulation
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