2. Academic Validation
  3. PR Domain-containing Protein 7 (PRDM7) Is a Histone 3 Lysine 4 Trimethyltransferase

PR Domain-containing Protein 7 (PRDM7) Is a Histone 3 Lysine 4 Trimethyltransferase

  • J Biol Chem. 2016 Jun 24;291(26):13509-19. doi: 10.1074/jbc.M116.721472.
Levi L Blazer 1,  Evelyne Lima-Fernandes 1,  Elisa Gibson 1,  Mohammad S Eram 1,  Peter Loppnau 1,  Cheryl H Arrowsmith 2,  Matthieu Schapira 3,  Masoud Vedadi 4
Affiliations

Affiliations

  • 1 From the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7.
  • 2 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.
  • 3 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.
  • 4 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 [email protected].
PMID: 27129774 DOI: 10.1074/jbc.M116.721472
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.

Keywords

epigenetics; histone methylation; histone modification; substrate specificity; zinc finger.

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