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Title: Mouse MORC3 is a GHKL ATPase involved in gene silencing and localizes to H3K4me3 marked chromatin      
keywords:
Epigenomics
ID:
PRJNA313086
description:
Microrchidia (MORC) proteins are GHKL ATPases that function in gene silencing in multiple organisms. Animal MORCs also contain CW-type zinc finger domains, which are known to bind to modified histones. We identified mouse MORC3 in a mutant screen for factors required for transgene silencing. We also found that MORC3 localizes to promoters marked by H3K4 trimethylation (H3K4me3) throughout the genome, consistent with its binding to H3K4me3 in vitro. We solved the crystal structure of the MORC3 ATPase-CW domain bound to the nucleotide analog AMPPNP and in complex with a H3K4me3 peptide. The CW domain uses an aromatic cage to bind trimethylated Lys4 and forms extensive hydrogen bonds with the H3 tail. We used native mass spectrometry to show that this region forms ATP dependent dimers, and that dimer formation is enhanced in the presence of non-hydrolyzable ATP analogs. Our work sheds light on aspects of the molecular function of MORC3 and suggests a counterintuitive role of MORC3 in both binding to active promoters and regulating gene silencing. Overall design: ChIP-seq study on 6 Samples.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA313086
authentication:
none
authorization:
none
ID:
pmid:27528681
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject