title: Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF.
abstract: HP1 proteins are transcriptional regulators that, like histones, are targets for post-translational modifications defining an HP1-mediated subcode. HP1γ has multiple phosphorylation sites, including serine 83 (S83) that marks it to sites of active transcription. In a guinea pig model for Shigella enterocolitis, we observed that the defective type III secretion mxiD Shigella flexneri strain caused more HP1γ phosphorylation in the colon than the wild-type strain. Shigella interferes with HP1 phosphorylation by injecting the phospholyase OspF. This effector interacts with HP1γ and alters its phosphorylation at S83 by inactivating ERK and consequently MSK1, a downstream kinase. MSK1 that here arises as a novel HP1γ kinase, phosphorylates HP1γ at S83 in the context of an MSK1-HP1γ complex, and thereby favors its accumulation on its target genes. Genome-wide transcriptome analysis reveals that this mechanism is linked to up-regulation of proliferative gene and fine-tuning of immune gene expression. Thus, in addition to histones, bacteria control host transcription by modulating the activity of HP1 proteins, with potential implications in transcriptional reprogramming at the mucosal barrier.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Unité INSERM 786 Institut Pasteur, Paris, France.
authors.forename: Habiba
authors.initials: H
authors.lastname: Harouz
authors.affiliation: Department of Biologie du Développement et Cellules Souches, Unité de Régulation Epigénétique, Institut Pasteur, Paris, France URA2578 CNRS, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rachez
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Unité INSERM 786 Institut Pasteur, Paris, France.
authors.forename: Benoit M
authors.initials: BM
authors.lastname: Meijer
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Unité INSERM 786 Institut Pasteur, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Marteyn
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Unité INSERM 786 Institut Pasteur, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Donnadieu
authors.affiliation: Equipe Epigénétique, différenciation cellulaire et cancer IRCM, Montpellier, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Cammas
authors.affiliation: Department of Biologie du Développement et Cellules Souches, Unité de Régulation Epigénétique, Institut Pasteur, Paris, France URA2578 CNRS, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Unité INSERM 786 Institut Pasteur, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Sansonetti
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Unité INSERM 786 Institut Pasteur, Paris, France laurence.arbibe@inserm.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Arbibe
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D019757:Carbon-Oxygen Lyases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004760:Enterocolitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D055106:Genome-Wide Association Study; D006168:Guinea Pigs; D051379:Mice; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D012763:Shigella flexneri / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002868:Chromosomal Proteins, Non-Histone; D000090266:Chromobox Protein Homolog 5; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D048049:Extracellular Signal-Regulated MAP Kinases; D019757:Carbon-Oxygen Lyases
keywords: CBX3; Heterochromatin protein 1; MSK1; Shigella; colon