title: PR Domain-containing Protein 7 (PRDM7) Is a Histone 3 Lysine 4 Trimethyltransferase.
abstract: PR domain-containing protein 7 (PRDM7) is a primate-specific histone methyltransferase that is the result of a recent gene duplication of PRDM9. The two proteins are highly homologous, especially in the catalytic PR/SET domain, where they differ by only three amino acid residues. Here we report that PRDM7 is an efficient methyltransferase that selectively catalyzes the trimethylation of H3 lysine 4 (H3K4) both in vitro and in cells. Through selective mutagenesis we have dissected the functional roles of each of the three divergent residues between the PR domains of PRDM7 and PRDM9. These studies indicate that after a single serine to tyrosine mutation at residue 357 (S357Y), PRDM7 regains the substrate specificities and catalytic activities similar to its evolutionary predecessor, including the ability to efficiently methylate H3K36.
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Levi L
authors.initials: LL
authors.lastname: Blazer
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lima-Fernandes
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gibson
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Eram
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Peter
authors.initials: P
authors.lastname: Loppnau
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, the Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, and.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, the Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Schapira
authors.affiliation: From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, the Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada m.vedadi@utoronto.ca.
authors.forename: Masoud
authors.initials: M
authors.lastname: Vedadi
mesh_terms: D019943:Amino Acid Substitution; D020440:Gene Duplication; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D016296:Mutagenesis; D020125:Mutation, Missense; D013379:Substrate Specificity
chemical_list: D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; C000602307:PRDM7 protein, human; C544431:PRDM9 protein, human
keywords: epigenetics; histone methylation; histone modification; substrate specificity; zinc finger