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Shigella flexneri targets the HP 1γ subcode through the phosphothreonine lyase O sp F
Author(s) -
Harouz Habiba,
Rachez Christophe,
Meijer Benoit M,
Marteyn Benoit,
Donnadieu Françoise,
Cammas Florence,
Muchardt Christian,
Sansonetti Philippe,
Arbibe Laurence
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201489244
Subject(s) - biology , shigella flexneri , phosphorylation , effector , microbiology and biotechnology , kinase , gene , genetics , escherichia coli
HP 1 proteins are transcriptional regulators that, like histones, are targets for post‐translational modifications defining an HP 1‐mediated subcode. HP 1γ has multiple phosphorylation sites, including serine 83 (S83) that marks it to sites of active transcription. In a guinea pig model for Shigella enterocolitis, we observed that the defective type III secretion mxiD Shigella flexneri strain caused more HP 1γ phosphorylation in the colon than the wild‐type strain. Shigella interferes with HP 1 phosphorylation by injecting the phospholyase OspF. This effector interacts with HP 1γ and alters its phosphorylation at S83 by inactivating ERK and consequently MSK 1, a downstream kinase. MSK 1 that here arises as a novel HP 1γ kinase, phosphorylates HP 1γ at S83 in the context of an MSK 1‐ HP 1γ complex, and thereby favors its accumulation on its target genes. Genome‐wide transcriptome analysis reveals that this mechanism is linked to up‐regulation of proliferative gene and fine‐tuning of immune gene expression. Thus, in addition to histones, bacteria control host transcription by modulating the activity of HP 1 proteins, with potential implications in transcriptional reprogramming at the mucosal barrier.