4.7 Article

Legionella pneumophila Effector RomA Uniquely Modifies Host Chromatin to Repress Gene Expression and Promote Intracellular Bacterial Replication

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CELL HOST & MICROBE
卷 13, 期 4, 页码 395-405

出版社

CELL PRESS
DOI: 10.1016/j.chom.2013.03.004

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资金

  1. Institut Carnot-Pasteur MI
  2. Fondation pour la Recherche Medicale (FRM)
  3. French Region Ile de France (DIM Malinf)
  4. project FunGen (ERA-Net PathoGenoMics) [ANR-08-PATH-002-02]
  5. Institut Pasteur
  6. Institut National du Cancer
  7. FRM
  8. European Research Council (ERC-stg)
  9. Association pour la Recherche sur le Cancer (ARC)
  10. [ANR-10-LABX-62-IBEID]

向作者/读者索取更多资源

Histone posttranslational modifications control eukaryotic gene expression and regulate many biological processes including immunity. Pathogens alter host epigenetic control to aid pathogenesis. We find that the intracellular bacterial pathogen Legionella pneumophila uses a Dot/Icm type IV secreted effector, RomA, to uniquely modify the host chromatin landscape. RomA, a SET domain-containing methyltransferase, trimethylates K14 of histone H3, a histone mark not previously described in mammals. RomA localizes to the infected cell nucleus where it promotes a burst of H3K14 methylation and consequently decreases H3K14 acetylation, an activating histone mark, to repress host gene expression. ChIP-seq analysis identified 4,870 H3K14 methylated promoter regions, including innate immune genes. Significantly reduced replication of a RomA-deleted strain in host cells was trans-complemented by wild-type, but not by catalytically inactive, RomA. Thus, a secreted L. pneumophila effector targets the host cell nucleus and modifies histones to repress gene expression and promote efficient intracellular replication.

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