Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis.
Histone modifications are critical in regulating gene expression, cell cycle, cell proliferation, and development. Relatively few studies have investigated whether Helicobacter pylori, the major cause of human gastric diseases, affects histone modification. We therefore investigated the effects of H...
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Public Library of Science (PLoS)
2010-04-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009875&type=printable |
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| author | Song-Ze Ding Wolfgang Fischer Maria Kaparakis-Liaskos George Liechti D Scott Merrell Patrick A Grant Richard L Ferrero Sheila E Crowe Rainer Haas Masanori Hatakeyama Joanna B Goldberg |
| author_facet | Song-Ze Ding Wolfgang Fischer Maria Kaparakis-Liaskos George Liechti D Scott Merrell Patrick A Grant Richard L Ferrero Sheila E Crowe Rainer Haas Masanori Hatakeyama Joanna B Goldberg |
| author_sort | Song-Ze Ding |
| collection | DOAJ |
| description | Histone modifications are critical in regulating gene expression, cell cycle, cell proliferation, and development. Relatively few studies have investigated whether Helicobacter pylori, the major cause of human gastric diseases, affects histone modification. We therefore investigated the effects of H. pylori infection on histone modifications in a global and promoter-specific manner in gastric epithelial cells. Infection of gastric epithelial cells by wild-type H. pylori induced time- and dose-dependent dephosphorylation of histone H3 at serine 10 (H3 Ser10) and decreased acetylation of H3 lysine 23, but had no effects on seven other specific modifications. Different cag pathogenicity island (PAI)-containing-clinical isolates showed similar abilities to induce H3 Ser10 dephosphorylation. Mutation of cagA, vacA, nonphosphorylateable CagA mutant cagA(EPISA), or disruption of the flagella showed no effects, while deletion of the entire cagPAI restored the H3 Ser10 phosphorylation to control levels. Analysis of 27 cagPAI mutants indicated that the genes that caused H3 Ser10 dephosphorylation were similar to those that were previously found to induce interleukin-8, irrespective of CagA translocation. This effect was independent of ERK or p38 pathways and type I interferon signaling. Additionally, c-Jun and hsp70 gene expression was associated with this histone modification. These results demonstrate that H. pylori alters histone modification and host response via a cagA-, vacA-independent, but cagPAI-dependent mechanisms, which contribute to its persistent infection and pathogenesis. |
| format | Article |
| id | doaj-art-5e6dee9faca74dd89a92655f15def404 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2010-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-5e6dee9faca74dd89a92655f15def4042025-08-20T03:07:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e987510.1371/journal.pone.0009875Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis.Song-Ze DingWolfgang FischerMaria Kaparakis-LiaskosGeorge LiechtiD Scott MerrellPatrick A GrantRichard L FerreroSheila E CroweRainer HaasMasanori HatakeyamaJoanna B GoldbergHistone modifications are critical in regulating gene expression, cell cycle, cell proliferation, and development. Relatively few studies have investigated whether Helicobacter pylori, the major cause of human gastric diseases, affects histone modification. We therefore investigated the effects of H. pylori infection on histone modifications in a global and promoter-specific manner in gastric epithelial cells. Infection of gastric epithelial cells by wild-type H. pylori induced time- and dose-dependent dephosphorylation of histone H3 at serine 10 (H3 Ser10) and decreased acetylation of H3 lysine 23, but had no effects on seven other specific modifications. Different cag pathogenicity island (PAI)-containing-clinical isolates showed similar abilities to induce H3 Ser10 dephosphorylation. Mutation of cagA, vacA, nonphosphorylateable CagA mutant cagA(EPISA), or disruption of the flagella showed no effects, while deletion of the entire cagPAI restored the H3 Ser10 phosphorylation to control levels. Analysis of 27 cagPAI mutants indicated that the genes that caused H3 Ser10 dephosphorylation were similar to those that were previously found to induce interleukin-8, irrespective of CagA translocation. This effect was independent of ERK or p38 pathways and type I interferon signaling. Additionally, c-Jun and hsp70 gene expression was associated with this histone modification. These results demonstrate that H. pylori alters histone modification and host response via a cagA-, vacA-independent, but cagPAI-dependent mechanisms, which contribute to its persistent infection and pathogenesis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009875&type=printable |
| spellingShingle | Song-Ze Ding Wolfgang Fischer Maria Kaparakis-Liaskos George Liechti D Scott Merrell Patrick A Grant Richard L Ferrero Sheila E Crowe Rainer Haas Masanori Hatakeyama Joanna B Goldberg Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS ONE |
| title | Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. |
| title_full | Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. |
| title_fullStr | Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. |
| title_full_unstemmed | Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. |
| title_short | Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. |
| title_sort | helicobacter pylori induced histone modification associated gene expression in gastric epithelial cells and its implication in pathogenesis |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009875&type=printable |
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