title: Targeting of chromatin readers: a novel strategy used by theShigella flexnerivirulence effector OspF to reprogram transcription.
abstract: Shigella flexneri, a gram-negative bacterium responsible of bacillary dysentery, uses multiple strategies to overcome host immune defense. We have decrypted how this bacterium manipulates host-cell chromatin binders to take control of immune gene expression. We found that OspF, an injected virulence factor previously identified as a repressor of immune gene expression, targets the chromatin reader HP1γ. Heterochromatin Protein 1 family members specifically recognize and bind histone H3 methylated at Lys 9. Although initially identified as chromatin-associated transcriptional silencers in heterochromatin, their location in euchromatin indicates an active role in gene expression. Notably, HP1γ phosphorylation at Serine 83 defines a subpopulation exclusively located to euchromatin, targeted to the site of transcriptional elongation. We showed that OspF directly interacts with HP1γ, and causes HP1 dephosphorylation, suggesting a model in which this virulence effector "uses" HP1 proteins as beacons to target and repress immune gene expression (Harouz,et al.EMBO J (2014)). OspF alters HP1γ phosphorylation mainly by inactivating the Erk-activated kinase MSK1, spotlighting it as a new HP1 kinase.In vivo, infectious stresses trigger HP1γ phosphorylation in the colon, principally in thelamina propriaand the intestinal crypts. Several lines of evidence suggest that HP1 proteins are modified as extensively as histones, and decrypting the impact of these HP1 post-translational modifications on their transcriptional activitiesin vivowill be the next challenges to be taken up.
authors.affiliation: Department of Immunology, Infectiology and Hematology, Institut Necker-Enfants Malades (INEM), INSERM U1151, CNRS UMR 8253, Université Paris Descartes, Paris, France.
authors.forename: Habiba
authors.initials: H
authors.lastname: Harouz
authors.affiliation: Department of Immunology, Infectiology and Hematology, Institut Necker-Enfants Malades (INEM), INSERM U1151, CNRS UMR 8253, Université Paris Descartes, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rachez
authors.affiliation: Department of Immunology, Infectiology and Hematology, Institut Necker-Enfants Malades (INEM), INSERM U1151, CNRS UMR 8253, Université Paris Descartes, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Meijer
authors.affiliation: Department of Immunology, Infectiology and Hematology, Institut Necker-Enfants Malades (INEM), INSERM U1151, CNRS UMR 8253, Université Paris Descartes, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
authors.affiliation: Department of Immunology, Infectiology and Hematology, Institut Necker-Enfants Malades (INEM), INSERM U1151, CNRS UMR 8253, Université Paris Descartes, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Arbibe
keywords: Heterochromatin protein 1; OspF; Shigella; epigenetic; immune gene