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UBC9‐mediated sumoylation of PR‐Set7 is involved in regulation of gene repression
Author(s) -
Spektor Tanya Magazinnik,
Rice Judd Christopher
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.456.12
Subject(s) - sumo protein , psychological repression , derepression , histone h4 , chemistry , histone , microbiology and biotechnology , epigenetics , histone methyltransferase , methyltransferase , histone h3 , ubiquitin , biology , biochemistry , gene , methylation , gene expression
The PR‐Set7/KMT5A histone methyltransferase and its mark, histone H4 lysine 20 monomethylation (H4K20me1), have been implicated in transcriptional repression, however, the exact molecular mechanism leading to this biological outcome remains unclear. Biochemical purification of PR‐Set7 reveals that it is part of a large multi‐protein complex. We hypothesized that identification of PR‐Set7‐associated proteins would provide important insights into the role of PR‐Set7 in gene repression. Yeast two‐hybrid screen revealed a novel interaction between PR‐Set7 and the sumoylation‐conjugation enzyme, UBC9. Additional studies demonstrated that direct interaction with UBC9 is mediated by the N‐terminal (non‐catalytic) domain of PR‐Set7. Furthermore, we discovered that PR‐Set7 is covalently modified specifically with SUMO‐1 and that this occurs in an ARIP3, E3 ligase‐dependent manner in vivo . Importantly, depletion of UBC9 in cells resulted in the derepression of PR‐Set7 target genes strongly suggesting that sumoylation by UBC9 is required for the normal repressive effects of the PR‐Set7 H4K20 monomethyltransferase.