Figure 5.

Species-Specific Adaptation of Promoters to Accommodate the Different Relationships between DNA Properties and DNA Methylation

(A) For this chart, 112 mouse promoter CGRs were selected that were orthologous to methylated human CGRs from ESCs with length >1 kb and CpG density >1.0. The graph to the left shows the corresponding 87 orthologous mouse promoters that were unmethylated in mouse ESCs, numbered and colored by CpG density as described in the key at right; 52 of these mouse ortholog promoters retain high CpG densities that are resistant to DNA methylation in mice. The right graph shows the 25 mouse promoters that were methylated in mouse ESCs similarly labeled and colored; the CpG densities of these promoters are consistently lower than those of their human orthologs, providing an explanation for their ability to be methylated in mouse cells. The very low (<0.55) CpG density group reflects genes for which a mouse ortholog exists, but which have no DNA region that fulfills the minimum criteria of a CGR within 500 bp of the transcription start site (TSS). DNA methylation at very low regions was calculated by averaging all CpGs within 500 bp of the TSS.

(B) Of the 52 mouse promoters from (A) that retain the high CpG densities observed with their human orthologs (and therefore are unmethylated in mice because CGRs with these DNA properties are almost never methylated), 27 were found to be silent in mouse ESCs (<0.5 RPKM). H3K27me3 levels are shown for these 27 promoters, suggesting that H3K27me3 may contribute to the silencing of these “methylation-resistant” mouse promoters.