Histone modifications induced by a family of bacterial toxins.
Upon infection, pathogens reprogram host gene expression. In eukaryotic cells, genetic reprogramming is induced by the concerted activation/repression of transcription factors and various histone modifications that control DNA accessibility in chromatin. We report here that the bacterial pathogen Listeria monocytogenes induces a dramatic dephosphorylation of histone H3 as well as a deacetylation of histone H4 during early phases of infection. This effect is mediated by the major listerial toxin listeriolysin O in a pore-forming-independent manner. Strikingly, a similar effect also is observed with other toxins of the same family, such as Clostridium perfringens perfringolysin and Streptococcus pneumoniae pneumolysin. The decreased levels of histone modifications correlate with a reduced transcriptional activity of a subset of host genes, including key immunity genes. Thus, control of epigenetic regulation emerges here as an unsuspected function shared by several bacterial toxins, highlighting a common strategy used by intracellular and extracellular pathogens to modulate the host response early during infection.
Hamon
Mélanie Anne
MA
Unité des Interactions Bactéries-Cellules, Unité de Régulation pigénétique, and Génopole, Plate-forme 2, Institut Pasteur, F-75015 Paris, France.
Batsché
Eric
E
Régnault
Béatrice
B
Tham
To Nam
TN
Seveau
Stéphanie
S
Muchardt
Christian
C
Cossart
Pascale
P
D000107:Acetylation; D001427:Bacterial Toxins / Q000737:chemistry*; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008089:Listeria monocytogenes / Q000502:physiology; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D001427:Bacterial Toxins; D006657:Histones