title: Histone H3K36 trimethylation is essential for multiple silencing mechanisms in fission yeast.
abstract: In budding yeast, Set2 catalyzes di- and trimethylation of H3K36 (H3K36me2 and H3K36me3) via an interaction between its Set2-Rpb1 interaction (SRI) domain and C-terminal repeats of RNA polymerase II (Pol2) phosphorylated at Ser2 and Ser5 (CTD-S2,5-P). H3K36me2 is sufficient for recruitment of the Rpd3S histone deacetylase complex to repress cryptic transcription from transcribed regions. In fission yeast, Set2 is also responsible for H3K36 methylation, which represses a subset of RNAs including heterochromatic and subtelomeric RNAs, at least in part via recruitment of Clr6 complex II, a homolog of Rpd3S. Here, we show that CTD-S2P-dependent interaction of fission yeast Set2 with Pol2 via the SRI domain is required for formation of H3K36me3, but not H3K36me2. H3K36me3 silenced heterochromatic and subtelomeric transcripts mainly through post-transcriptional and transcriptional mechanisms, respectively, whereas H3K36me2 was not enough for silencing. Clr6 complex II appeared not to be responsible for heterochromatic silencing by H3K36me3. Our results demonstrate that H3K36 methylation has multiple outputs in fission yeast; these findings provide insights into the distinct roles of H3K36 methylation in metazoans, which have different enzymes for synthesis of H3K36me1/2 and H3K36me3.
authors.affiliation: Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Suzuki
authors.affiliation: Department of Biochemistry, Shimane University School of Medicine, Izumo 693-8501, Japan PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi 332-0012, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8562, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Advanced ICT Research Institute, National Institute of Information and Communications Technology, Kobe 651-2492, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Chikashige
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hiraoka
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Graduate School of Life Science, Hokkaido University, Sapporo 001-0021, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nagao
authors.affiliation: Graduate School of Life Science, Hokkaido University, Sapporo 001-0021, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Obuse
authors.affiliation: Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takahata
authors.affiliation: Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan yota@sci.hokudai.ac.jp.
authors.forename: Yota
authors.identifier: 0000-0002-2023-1303
authors.initials: Y
authors.lastname: Murakami
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics / Q000648:ultrastructure; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal; D006570:Heterochromatin / Q000235:genetics / Q000648:ultrastructure; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000502:physiology; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism; D020871:RNA Stability; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000502:physiology; D016615:Telomere / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D006570:Heterochromatin; D006657:Histones; D029702:Schizosaccharomyces pombe Proteins; D011495:Histone-Lysine N-Methyltransferase; C527202:Set2 protein, S pombe; D012319:RNA Polymerase II