Bioinformatics of CYP2E1 CpG intron methylation sites and application to HAR1-RELN sequence analysis

The CYP2E1 CpG methylation sites in the first intron (site +626 to +742 from the starting ATG) as reported in a 2015 epigenetics psychiatry study were analyzed from a bioinformatics perspective. The studied sequences for human, monkey, dog and cow showed a high correlation (R-sq > 0.99) between CpG content and mononucleotide entropy. A comparably high correlation (R-sq > 0.95) was also found between the first exon sequences and mononucleotide entropy. These findings lend support to the hypothesis that CpG content is proportional to nucleotide availability when the latter quantity is computed as information entropy. To probe the nature of CpG sites in HAR1, a comparative study was conducted using the known promoter methylation regions in RELN and EGFR sequences. The observed high correlation (R-sq = 0.999) suggests that the eight CpG sites in HAR1 may function as human-specific gene expression controller sites since the equivalent chimp sequence has no CpG sites. A general scheme using randomly selected CpG methylation sites that precede the starting ATG codon is discussed with regard to fractal dimension modeling. Furthermore, an analysis of the studied RELN homolog CDS sequences for human, bovine, mouse and rat showed a high correlation of dinucleotide entropy with free energy (R > 0.9), consistent with the high correlation (R > 0.9) observed in a similar analysis of the studied pro-BDNF homolog CDS sequences for human, chimp, mouse and rat.