Figure 7

Analysis of hypomethylation-associated factors. (A) R-loop formation potential in distinct CpG island (CGI) groups. The percentages of methylated (blue) versus unmethylated (red) CGIs within each category are shown. The effect of R-loop formation potential on DNA methylation is small once CGIs have been stratified into promoter associated (PA) versus intragenic groups. (B) Pairwise significant interaction/correlation network of hypomethylation-associated factors. The numbers from 1 to 5 (red) indicate the rank of the factors based on the reduction in deviance compared to the null model which represents their power in predicting CGI methylation state (1 = most predictive value; Table S4). Significant interactions between factors are represented by black lines labelled with the Bonferroni multiple testing corrected chi-square P value (see Table S5 for a complete list of pairwise interaction statistics). Factors that are correlated with an absolute Pearson correlation coefficient (CC) >0.29 (the maximum correlation observed between any of the factors and the methylation state) are connected by grey lines labelled with the CC (see Table S3 for a complete list of pairwise CCs). (C) The proposed model of how a methylation-free state is established and maintained at oocyte-unmethylated CGIs. We propose that chromatin remodelling (Swi/Snf via Arid1b) and histone acetyltransferase (Kat5) complexes protect the CGI sequence from de novo methylation by keeping the CGI nucleosome-free and, therefore, free of the preferred substrate of Dnmt3a/l. They, in turn, are recruited to the CGI by E2f1 and/or E2f2 bound to the CGCGC recognition site in the CGI sequence.