An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses

Nat Immunol. 2007 Jan;8(1):47-56. doi: 10.1038/ni1423. Epub 2006 Dec 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / physiology*
  • Cell Line, Tumor
  • Cells, Cultured
  • Chromatin / genetics*
  • HeLa Cells
  • Humans
  • Immunity
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • NF-kappa B / metabolism*
  • Shigella flexneri / immunology*
  • Transcription, Genetic* / immunology


  • Bacterial Outer Membrane Proteins
  • Chromatin
  • NF-kappa B

Associated data

  • GEO/GSE6082