Distinct Methylation ofIFNGin the Gut
- 1 July 2009
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Interferon & Cytokine Research
- Vol. 29 (7), 407-414
- https://doi.org/10.1089/jir.2008.0109
Abstract
Mucosal expression of proinflammatory cytokines plays a pivotal role in inflammatory bowel disease (IBD) pathogenesis. Epigenetic remodeling of chromatin via DNA methylation regulates gene expression. In this study, IFNG DNA methylation was analyzed within the mucosal compartment in both normal and IBD populations and compared to its peripheral counterparts. Overall IFNG methylation (across eight CpG sites) was significantly lower in lamina propria (LP) T cells compared to peripheral blood (PB) T cells. No methylation differences were detected when comparing PB T derived from normal to IBD patients. However, LP T-cell DNA derived from IBD patients displayed different levels of IFNG methylation of the upstream regulatory regions compared to DNA from normal controls. In fact, IFNG DNA promoter methylation levels functionally correlate with IFNG mRNA expression in unstimulated T cells, using quantitative real-time PCR. A 5% decrease in promoter methylation status is associated with nearly a 3-fold increase in IFNG expression. Likewise, methylation of the single −54 bp IFNG SnaB1 site strongly inhibited IFNG promoter expression. These results suggest that the epigenetic methylation status of IFNG may play a mechanistic role in the modulation of cytokine secretion in the mucosa.Keywords
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