Helicobacter pylori regulates p21WAF1 by histone H4 acetylation

Helicobacter pylori are bacteria that colonize the stomach persistently, which confers risk of serious diseases, including peptic ulceration and gastric neoplasia. Aberrant expression of cell cycle control proteins has been demonstrated in H. pylori infected gastric epithelial cells, suggesting that perturbation of the cell cycle plays a role in the pathogenesis of various H. pylori associated diseases. In this study, we investigate the modulation of the cell cycle control protein p21WAF1 by H. pylori in the gastric carcinoma cell line NCI-N87 and in primary gastric cells derived from healthy tissue. We observed an up-regulation of p21WAF1 in both NCI-N87 and primary cells. Chromatin immunoprecipitation analysis revealed that the increased expression of p21WAF1 induced by H. pylori is associated with the release of HDAC-1 from the p21WAF1 promoter and hyper-acetylation of histone H4. The elucidation of the epigenetic regulation of p21WAF1 by H. pylori may help to dissect the pathogenetic mechanisms underlying the development and progression of H. pylori associated diseases.