title: Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification.
abstract: Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes. Here we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that fibrillarin is the orthologue enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows that this modification is exclusively enriched over the 35S ribosomal DNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (facilitator of chromatin transcription) complex. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and increased transcription at the ribosomal DNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.
authors.affiliation: 1] Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Tessarz
authors.affiliation: 1] Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Santos-Rosa
authors.affiliation: 1] Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Sam C
authors.initials: SC
authors.lastname: Robson
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
authors.forename: Kathrine B
authors.initials: KB
authors.lastname: Sylvestersen
authors.affiliation: 1] Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [3] Department of Biochemistry and Microbiology, University of Victoria, 3800 Finnerty Road, Victoria, British Columbia V8P 5C2, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Nelson
authors.affiliation: Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nielsen
authors.affiliation: 1] Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Tony
authors.initials: T
authors.lastname: Kouzarides
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D002466:Cell Nucleolus / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics; D004843:Epistasis, Genetic; D005973:Glutamine / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012313:RNA / Q000378:metabolism; D012318:RNA Polymerase I / Q000378:metabolism*; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D006657:Histones; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C064793:NOP1 protein, S cerevisiae; D009687:Nuclear Proteins; D009707:Nucleosomes; D020718:Ribonucleoproteins, Small Nucleolar; D029701:Saccharomyces cerevisiae Proteins; C047458:fibrillarin; D005973:Glutamine; D012313:RNA; D008780:Methyltransferases; D012318:RNA Polymerase I; D000409:Alanine