Mapping of DNA methylation-sensitive cellular processes in gingival fibroblasts using the DNMT inhibitor decitabine

Epigenetic changes in DNA methylation are involved in periodontitis pathogenesis and recent studies indicate that DNA methyltransferase (DNMT) inhibitors may protect against bone resorption and disruption of the epithelial barrier. To assess the impact of DNMT inhibition on gingival fibroblasts (GFs), cells were cultured with decitabine (5-aza-2’-deoxycytidine, DAC) for 12 days to induce DNA hypomethylation. Analysis of DAC-induced genes in resting or P. gingivalis-infected GFs identified by RNA sequencing revealed increased expression of CCL20, CCL5, CCL8, CCL13, TNF, IL1A, IL18, IL33, and CSF3, and showed that the most affected processes were related to immune and inflammatory responses. In contrast, the genes downregulated by DAC were associated with extracellular matrix and collagen fibril organization. Comparative gene expression profiling analysis of RNA-seq data for GFs that were subjected to 12-day culture with DMSO or DAC (5 μM) and then were either left untreated or were infected with P. gingivalis (MOI 20) for 4 h.