An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.
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.
Arbibe
Laurence
L
Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, F75724 Paris Cedex 15, France. arbibe@pasteur.fr
Kim
Dong Wook
DW
Batsche
Eric
E
Pedron
Thierry
T
Mateescu
Bogdan
B
Muchardt
Christian
C
Parsot
Claude
C
Sansonetti
Philippe J
PJ
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
D001425:Bacterial Outer Membrane Proteins; D002843:Chromatin; D016328:NF-kappa B