title: Trimethylation of histone H3 lysine 36 by human methyltransferase PRDM9 protein.
abstract: PRDM9 (PR domain-containing protein 9) is a meiosis-specific protein that trimethylates H3K4 and controls the activation of recombination hot spots. It is an essential enzyme in the progression of early meiotic prophase. Disruption of the PRDM9 gene results in sterility in mice. In human, several PRDM9 SNPs have been implicated in sterility as well. Here we report on kinetic studies of H3K4 methylation by PRDM9 in vitro indicating that PRDM9 is a highly active histone methyltransferase catalyzing mono-, di-, and trimethylation of the H3K4 mark. Screening for other potential histone marks, we identified H3K36 as a second histone residue that could also be mono-, di-, and trimethylated by PRDM9 as efficiently as H3K4. Overexpression of PRDM9 in HEK293 cells also resulted in a significant increase in trimethylated H3K36 and H3K4 further confirming our in vitro observations. Our findings indicate that PRDM9 may play critical roles through H3K36 trimethylation in cells.
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Eram
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Susan P
authors.initials: SP
authors.lastname: Bustos
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lima-Fernandes
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Alena
authors.initials: A
authors.lastname: Siarheyeva
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Senisterra
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Taraneh
authors.initials: T
authors.lastname: Hajian
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Irene
authors.initials: I
authors.lastname: Chau
authors.affiliation: Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Shili
authors.initials: S
authors.lastname: Duan
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Dombrovski
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Schapira
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7; Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.affiliation: Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8. Electronic address: m.vedadi@utoronto.ca.
authors.forename: Masoud
authors.initials: M
authors.lastname: Vedadi
mesh_terms: D002151:Calorimetry; D019175:DNA Methylation; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D013379:Substrate Specificity
chemical_list: D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human; D008239:Lysine
keywords: Cancer; Enzyme Inhibitors; Enzyme Kinetics; Epigenetics; Histone Methylation; Methyltransferase