Title: Helicobacter pylori Infection Alters Expression of Histone Modification Complex Components
Authors: Rebecca FitzGerald, Malini Devapal, Volga Saini, John Hickey, Deirdre McNamara, Sinéad M Smith.
Affiliations: School of Medicine, Trinity College Dublin; School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin.
Introduction: The Polycomb repressive complex 2 (PRC2) tri-methylates and KDM6B de-methylates histone H3 on lysine 27 (H3K27). Aberrant histone methylation alters gene expression and is linked to disease.
Aim: Investigate PRC2 and KDM6B expression during H. pylori infection.
Methods: qPCR was performed to monitor H. pylori-mediated changes in expression of PRC2 component genes EZH2, EED and SUZ12 in MKN45 and AGS gastric epithelial cells and stomach biopsies from H. pylori-infected and uninfected patients. Expression of PRC2 components and KDM6B were measured in THP-1 macrophages infected with live or heat-inactivated H. pylori. Accumulation of RNA polymerase II (PolII) and H3K27me3 at gene loci was measured by chromatin immunoprecipitation (ChIP)-qPCR. The Student’s T-test and Mann-Whitney U-test identified significance (P<0.05) for cell culture and tissue results, respectively.
Results: H. pylori decreased expression of EZH2, EED and SUZ12 in AGS and MKN45 cells. A significant decrease (41%) in the median expression levels of EED was observed in the gastric mucosa of _H. pylori-_infected (N=21) versus uninfected (N=9) patients (P=0.03). EED and EZH2 expression was significantly reduced in H. pylori-infected THP-1 macrophages. KDM6B was significantly increased in THP-1 cells infected with live and heat inactivated H. pylori. Decreased expression of PRC2 components was associated with decreased accumulation of H3K27me3 and increased PolII at the transcriptional start site of Interleukin-8.
Conclusion: H. pylori inhibits expression of PRC2 components in gastric epithelial cells, macrophages and gastric mucosa and increases KDM6B expression in macrophages. H. pylori reduces levels of the repressive histone mark H3K27me3 at the Interleukin-8 gene.

**Title:** _Helicobacter pylori_ Infection Alters Expression of Histone Modification Complex Components
**Authors:** Rebecca FitzGerald, Malini Devapal, Volga Saini, John Hickey, Deirdre McNamara, Sinéad M Smith.
**Affiliations:** School of Medicine, Trinity College Dublin; School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin.
**Introduction:** The Polycomb repressive complex 2 (PRC2) tri-methylates and _KDM6B_ de-methylates histone H3 on lysine 27 (H3K27). Aberrant histone methylation alters gene expression and is linked to disease.
**Aim:** Investigate PRC2 and _KDM6B_ expression during _H. pylori_ infection.
**Methods:** qPCR was performed to monitor _H. pylori_-mediated changes in expression of PRC2 component genes _EZH2_, _EED_ and _SUZ12_ in MKN45 and AGS gastric epithelial cells and stomach biopsies from _H. pylori_-infected and uninfected patients. Expression of PRC2 components and _KDM6B_ were measured in THP-1 macrophages infected with live or heat-inactivated _H. pylori_. Accumulation of RNA polymerase II (PolII) and H3K27me3 at gene loci was measured by chromatin immunoprecipitation (ChIP)-qPCR. The Student’s T-test and Mann-Whitney U-test identified significance (P<0.05) for cell culture and tissue results, respectively.
**Results:** _H. pylori_ decreased expression of _EZH2_, _EED_ and _SUZ12_ in AGS and MKN45 cells. A significant decrease (41%) in the median expression levels of _EED_ was observed in the gastric mucosa of _H. pylori-_infected (N=21) versus uninfected (N=9) patients (P=0.03). _EED_ and _EZH2_ expression was significantly reduced in _H. pylori_-infected THP-1 macrophages. _KDM6B_ was significantly increased in THP-1 cells infected with live and heat inactivated _H. pylori_. Decreased expression of PRC2 components was associated with decreased accumulation of H3K27me3 and increased PolII at the transcriptional start site of Interleukin-8.
**Conclusion:** _H. pylori_ inhibits expression of PRC2 components in gastric epithelial cells, macrophages and gastric mucosa and increases _KDM6B_ expression in macrophages. _H. pylori_ reduces levels of the repressive histone mark H3K27me3 at the Interleukin-8 gene.

Inhibition of Polycomb Repressive Complex 2 expression and function by Helicobacter pylori.

Exploring the intricacies of host-pathogen communication is vital in order to understand why
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