Identification and characterization of a human MORC2 DNA binding region that is required for gene silencing.
Nikole L FendlerJimmy LyLuisa WelpHenning UrlaubSeychelle M VosPublished in: bioRxiv : the preprint server for biology (2024)
The eukaryotic microrchidia (MORC) protein family are DNA g yrase, H sp90, histidine k inase, Mut L (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 reduces its affinity for DNA and appears to 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.
Keyphrases
- dna binding
- transcription factor
- gene expression
- circulating tumor
- single molecule
- induced apoptosis
- endothelial cells
- cell free
- protein protein
- binding protein
- amino acid
- cell cycle arrest
- dna damage
- oxidative stress
- small molecule
- cell death
- dna methylation
- endoplasmic reticulum stress
- mass spectrometry
- big data
- circulating tumor cells
- pluripotent stem cells
- pi k akt