Additional file 8: of A functional SNP associated with atopic dermatitis controls cell type-specific methylation of the VSTM1 gene locus

Model on the potentiating effect of a regulatory CpG-SNP. A Conventional vs. regulatory CpG-SNPs. The methylation of CpG pairs results in the condensation of chromatin due to a tighter packaging of the histone-DNA complexes (open circle: non-methylated CpG, closed circle: methylated CpG). While a conventional CpG-SNP can assist this process by providing only one additional allele-dependent methylation site (middle panel), a regulatory CpG-SNP (such as rs612529) modulates the recruiting of CpG-modifying enzymes (right panel). In the case of rs612529, this seems to be mediated by the allele-specific binding of PU.1 to the T allele of the CpG-SNP. In monocytes PU.1 was reported to bind the demethylase Tet-2. B Potentiating effect. Recruitment of Tet-2 mediates the chromatin-opening by facilitating the demethylation of all CpG pairs in the vicinity. The epigenetic effect is allele-specific (T allele) and direction of the direction probably cell-type–dependent. (PDF 415 kb)