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The histone‐binding protein COPR5 is required for nuclear functions of the protein arginine methyltransferase PRMT5
Author(s) -
Lacroix Matthieu,
Messaoudi Selma El,
Rodier Geneviève,
Le Cam Aphonse,
Sardet Claude,
Fabbrizio Eric
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.45
Subject(s) - protein arginine methyltransferase 5 , histone h4 , histone methyltransferase , chromatin , biology , histone , microbiology and biotechnology , nuclear protein , chromatin remodeling , nucleosome , histone code , histone h3 , histone h1 , biochemistry , methyltransferase , methylation , gene , transcription factor
Protein arginine methyltransferase 5 (PRMT5) targets nuclear and cytoplasmic proteins. Here, we identified a nuclear protein, called cooperator of PRMT5 (COPR5), involved in the nuclear functions of PRMT5. COPR5 tightly binds to PRMT5, both in vitro and in living cells, but not to other members of the PRMT family. PRMT5 bound to COPR5 methylates histone H4 (R3) preferentially when compared with histone H3 (R8), suggesting that COPR5 modulates the substrate specificity of nuclear PRMT5‐containing complexes, at least towards histones. Markedly, recombinant COPR5 binds to the amino terminus of histone H4 and is required to recruit PRMT5 to reconstituted nucleosomes in vitro . Consistently, COPR5 depletion in cells strongly reduces PRMT5 recruitment on chromatin at the PRMT5 target gene cyclin E1 ( CCNE1 ) in vivo . Moreover, both COPR5 depletion and overexpression affect CCNE1 promoter expression. We propose that COPR5 is an important chromatin adaptor for PRMT5 to function on a subset of its target genes.