Influence of epigenetic modifications of the interleukin-10 promoter on IL10 gene expression.

Epigenetic modifications of DNA and its associated proteins influence gene expression. The -1087 interleukin-10 (IL10) gene polymorphism is associated with differences in IL10 expression. The objectives of this study were to analyze the effect of DNA methylation and histone modifications on IL10 gene expression, the differences in epigenetic modifications between GG and AA genotypes of the -1087 IL10 gene polymorphism, and the methylation pattern in the region close to the -1087 position. Using B cells obtained from subjects with GG and AA genotypes we demonstrated that treatment with histone deacetylase inhibitors and 5-aza-2-deoxycytidine resulted in an increase in the production of IL10 mRNA. The chromatin immunoprecipitation assay revealed that stimulation with lipopolysaccharide resulted in a higher fold increase in the acetylation of histone H4 and in the methylation of histone H3 for GG genotype cells than for AA genotype cells. The increase in acetylation of histone H3 was larger for AA genotype cells than for GG genotype cells. For unstimulated cells the acetylation and methylation of histone H3 were higher for GG genotype cells than for AA genotype cells, while AA genotype cells had a higher increase in acetylation of histone H4. DNA methylation assays revealed that the three CpG sites distal to the -1087 site were methylated in blood cells and gingival tissues.