title: The fission yeast Jmj2 reverses histone H3 Lysine 4 trimethylation.
abstract: Histone methylation regulates transcription, chromatin structure, and the epigenetic state of the cell. Recent studies identified the JmjC domain as a catalytic module for histone demethylation. Schizosaccharomyces pombe contains seven JmjC proteins, but it was unclear whether any of them functioned as histone demethylases. In this report, we show that the JmjC protein Jmj2, which is evolutionarily conserved from yeast to human, reversed trimethylated H3-Lys-4 to di- and mono-but not unmethylated products. Overexpression of Jmj2 but not a catalytically inactive mutant reduced H3-Lys-4 trimethylation levels in vivo and suppressed the toxicity caused by overexpression of the H3-Lys-4-me3-binding protein Yng1 in budding yeast. Genome-wide analysis showed that the loss of jmj2 was associated with an increase in the H3-Lys-4-me3 signal, which was enriched near the transcriptional start sites and the coding regions. At the mating-type locus, the loss of jmj2 or substitution of jmj2 with a catalytically inactive form is correlated with increased reporter gene transcription and H3-Lys-4-me3/2 levels, suggesting that Jmj2 and its demethylase activity may play a role in heterochromatin biology. Our findings identified a novel S. pombe histone demethylase with specificity toward di- and trimethylated histone H3-Lys-4 and a possible role in heterochromatin regulation.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Maite
authors.initials: M
authors.lastname: Huarte
authors.forename: Fei
authors.initials: F
authors.lastname: Lan
authors.forename: Taesoo
authors.initials: T
authors.lastname: Kim
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Vaughn
authors.forename: Mikel
authors.initials: M
authors.lastname: Zaratiegui
authors.forename: Robert A
authors.initials: RA
authors.lastname: Martienssen
authors.forename: Stephen
authors.initials: S
authors.lastname: Buratowski
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D017353:Gene Deletion; D016681:Genome, Fungal; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D006657:Histones; C522842:Jmj2 protein, S pombe; C093953:NMT1 protein, S pombe; D011994:Recombinant Proteins; D029702:Schizosaccharomyces pombe Proteins; D008239:Lysine