title: Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication.
abstract: Histone posttranslational modifications control eukaryotic gene expression and regulate many biological processes including immunity. Pathogens alter host epigenetic control to aid pathogenesis. We find that the intracellular bacterial pathogen Legionella pneumophila uses a Dot/Icm type IV secreted effector, RomA, to uniquely modify the host chromatin landscape. RomA, a SET domain-containing methyltransferase, trimethylates K14 of histone H3, a histone mark not previously described in mammals. RomA localizes to the infected cell nucleus where it promotes a burst of H3K14 methylation and consequently decreases H3K14 acetylation, an activating histone mark, to repress host gene expression. ChIP-seq analysis identified 4,870 H3K14 methylated promoter regions, including innate immune genes. Significantly reduced replication of a RomA-deleted strain in host cells was trans-complemented by wild-type, but not by catalytically inactive, RomA. Thus, a secreted L. pneumophila effector targets the host cell nucleus and modifies histones to repress gene expression and promote efficient intracellular replication.
authors.affiliation: Institut Pasteur, Unité Biologie des Bactéries Intracellulaires, Paris 75015, France.
authors.forename: Monica
authors.initials: M
authors.lastname: Rolando
authors.forename: Serena
authors.initials: S
authors.lastname: Sanulli
authors.forename: Christophe
authors.initials: C
authors.lastname: Rusniok
authors.forename: Laura
authors.initials: L
authors.lastname: Gomez-Valero
authors.forename: Clement
authors.initials: C
authors.lastname: Bertholet
authors.forename: Tobias
authors.initials: T
authors.lastname: Sahr
authors.forename: Raphael
authors.initials: R
authors.lastname: Margueron
authors.forename: Carmen
authors.initials: C
authors.lastname: Buchrieser
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D002843:Chromatin / Q000235:genetics* / Q000276:immunology; D004261:DNA Replication / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression / Q000235:genetics* / Q000276:immunology; D006657:Histones / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D016952:Legionella pneumophila / Q000235:genetics* / Q000276:immunology; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D014158:Transcription, Genetic / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins