title: An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.
abstract: Phosphorylation of histone H3 at Ser10 increases chromatin accessibility to transcription factor NF-kappaB on a subset of genes involved in immune responses. Here we report that a bacterial pathogen abrogated phosphorylation of histone H3 to 'shape' the transcriptional responses of infected host cells. We identify the Shigella flexneri protein effector OspF as a dually specific phosphatase that dephosphorylated mitogen-activated protein kinases in the nucleus, thus preventing histone H3 phosphorylation at Ser10 in a gene-specific way. That activity of OspF enabled shigella to block the activation of a subset of NF-kappaB-responsive genes, leading to compromised recruitment of polymorphonuclear leukocytes to infected tissues. S. flexneri has thus evolved the capacity to precisely modulate host cell epigenetic 'information' as a strategy for repressing innate immunity.
authors.affiliation: Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, F75724 Paris Cedex 15, France. arbibe@pasteur.fr
authors.forename: Laurence
authors.initials: L
authors.lastname: Arbibe
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Eric
authors.initials: E
authors.lastname: Batsche
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedron
authors.forename: Bogdan
authors.initials: B
authors.lastname: Mateescu
authors.forename: Christian
authors.initials: C
authors.lastname: Muchardt
authors.forename: Claude
authors.initials: C
authors.lastname: Parsot
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Sansonetti
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007109:Immunity; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology; D016328:NF-kappa B / Q000378:metabolism*; D012763:Shigella flexneri / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002843:Chromatin; D016328:NF-kappa B