Discovery and characterisation of the automethylation properties of PRDM9

Discovery and characterisation of the automethylation properties of PRDM9
Title:
Discovery and characterisation of the automethylation properties of PRDM9
Other Titles:
Biochemical Journal
DOI:
10.1042/BCJ20161067
Publication Date:
07 March 2017
Citation:
Biochemical Journal Mar 07, 2017, 474 (6) 971-982;
Abstract:
We have previously characterised the histone lysine methyltransferase properties of PRDM9, a member of the PRDM family of putative transcriptional regulators. PRDM9 displays broad substrate recognition and methylates a range of histone substrates, including octamers, core histone proteins, and peptides. In the present study, we show that PRDM9 performs intramolecular automethylation on multiple lysine residues localised to a lysine-rich region on the post-SET (suppressor of variegation 3–9, enhancer of zeste and trithorax) domain. PRDM9 automethylation is abolished by a single active-site mutation, C321P, also known to disrupt interactions with S-adenosylmethionine. We have taken an initial step towards tool compound generation through rational design of a substrate-mimic, peptidic inhibitor of PRDM9 automethylation. The discovery of automethylation in PRDM9 adds a new dimension to our understanding of PRDM9 enzymology.
License type:
PublisherCopyrights
Funding Info:
Agency for Science, Technology and Research Fast-Track Joint-Council Office Development Programme Grant [grant number 1134c001]
Description:
ISSN:
0264-6021
1470-8728
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