TBA (21W178)

Infection Alters Expression of Histone Modification Complex Components


R. FitzGerald, M. Devapal, V. Saini, J. Hickey, D. McNamara, S. M. Smith.


School of Medicine, Trinity College Dublin; School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin.


The Polycomb repressive complex 2 (PRC2) tri-methylates and KDM6B de-methylates histone H3 on lysine 27 (H3K27). Aberrant histone methylation is linked to disease.


Investigate PRC2 and KDM6B expression during ????. ???????????????????????? infection.


qPCR was performed to monitor ????. ????????????????????????-mediated changes in expression of PRC2 components ????????????2, ???????????? and ????????????12 in MKN45 and AGS gastric epithelial cells and stomach biopsies from ????. ????????????????????????-infected and uninfected patients. Expression of PRC2 components and KDM6B were measured in THP-1 macrophages infected with live or heat-inactivated ????. ????????????????????????. 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.


????. ???????????????????????? decreased expression of ????????????2, ???????????? and ????????????12 in AGS and MKN45 cells. A significant decrease (41%) in median expression levels of ???????????? was observed in the gastric mucosa of ????. ???????????????????????? infected (N=21) versus uninfected (N=9) patients (P=0.03). ????????????2 and ???????????? expression was significantly reduced in ????. ????????????????????????-infected THP-1 macrophages. ????????????6???? was significantly increased in THP-1 cells infected with live and heat inactivated ????. ????????????????????????. Decreased expression of PRC2 components was associated with decreased accumulation of H3K27me3 and increased PolII at the transcriptional start site of ????????????????????????????????????????????-8 gene.


????. ???????????????????????? alters expression of histone modification complex components and reduces levels of the repressive histone mark H3K27me3 at the ????????????????????????????????????????????-8 gene. Further studies will identify additional genes that are impacted by changes in H3K27 methylation during ????. ???????????????????????? pathogenesis.