Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells.
Inducible nitric oxide synthase (iNOS) expression is altered in gastrointestinal diseases. Helicobacter pylori (Hp) infection may have a critical role in iNOS disregulation. We undertook this study to investigate possible chromatin changes occurring early during iNOS gene activation as a direct consequence of Hp-gastric cells interaction. We show that Hp infection is followed by different expression and chromatin modifications in gastric cells including (1) activation of iNOS gene expression, (2) chromatin changes at iNOS promoter including decreased H3K9 methylation and increased H3 acetylation and H3K4 methylation levels, (3) selective release of methyl-CpG-binding protein 2 from the iNOS promoter. Moreover, we show that Hp-induced activation of iNOS is delayed, but not eliminated, by the treatment with LSD1 inhibitors. Our data suggest a role for specific chromatin-based mechanisms in the control of human iNOS gene expression upon Hp exposure.
Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Facoltà di Scienze Biotecnologiche and Facoltà di Farmacia, Università degli Studi di Napoli Federico II, via S. Pansini 5, 80131, Naples, Italy.
Tiziana
T
Angrisano
Francesca
F
Lembo
Silvia
S
Peluso
Simona
S
Keller
Lorenzo
L
Chiariotti
Raffaela
R
Pero
D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000166:cytology* / Q000378:metabolism; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*
D002843:Chromatin; D006657:Histones; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II