PXD050648

PXD050648 is an original dataset announced via ProteomeXchange.

Title	Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing
Description	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 is heavily phosphorylated in cells. Phosphorylation of MORC2 appears to reduce its affinity for DNA and exclude the protein from the nucleus. We observe that DNA binding by MORC2 reduces its ATPase activity and that MORC2 can topologically 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-13
AnnouncementXML	Submission_2025-05-13_06:04:05.941.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luisa Welp
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-15 03:40:32	ID requested
⏵ 1	2025-05-13 06:04:06	announced

Fendler NL, Ly J, Welp L, Lu D, Schulte F, Urlaub H, Vos SM, Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing. Nucleic Acids Res, 53(4):(2025) [pubmed]

10.1093/nar/gkae1273;

submitter keyword: MORC, DNA, gene silencing,human

Seychelle Vos
contact affiliation	Department of Biology, Massachusetts Institute of Technology, Building 68, 31 Ames St., Cambridge, MA 02139 Howard Hughes Medical Institute, Chevy Chase, MD
contact email	seyvos@mit.edu
lab head
Luisa Welp
contact affiliation	Max-Planck-Institute for Biophysical Chemistry
contact email	lwelp@gwdg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050648
     1. Label: PRIDE project
     2. Name: Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing