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Histone H4K20 monomethylation enables recombinant nucleosome methylation by PRMT1 in vitro.

Protein arginine methyltransferases (PRMTs) catalyze the transfer of methyl groups to specific arginine residues of histones and nonhistone proteins. There are nine members in the PRMT family (PRMT1 to PRMT9), and PRMT1 is a dominant member catalyzing majority of arginine methylation in the cell. However, none of the PRMTs is active with recombinant nucleosome as substrate in vitro. Here, we report the discovery of the first in class novel crosstalk between histone H4 lysine 20 (H4K20) monomethylation on nucleosome by SETD8 and histone H4 arginine 3 (H4R3) methylation by PRMT1 in vitro. Full kinetic characterization and mass spectrometry analysis indicated that PRMT1 is only active with recombinant nucleosomes monomethylated at H4K20 by SETD8. These data suggests that the level of activity of PRMT1 could potentially be regulated selectively by SETD8 in various pathways, providing a new approach for discovery of selective regulators of PRMT1 activity.

Date de publication
21 février 2023
Chercheur(euse)s
Li ASM, Homsi C, Bonneil E, Thibault P, Verreault A, Vedadi M
Référence PubMed
Biochim Biophys Acta Gene Regul Mech 2023;1866(2):194922
ID PubMed
36822575
Affiliation
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Drug Discovery Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.