DNA Methylation

Methylation is the addition of a methyl group (-CH₃). A methylation reaction is catalyzed by an enzyme called DNA methyltransferase. Methylation can occur in both histones and DNA. It is found in eukaryotic organisms. In mammals, DNA methylation primarily occurs at the 5’-carbon cytosine (C) bases that are adjacent to guanine (G) bases, resulting in 5’-methylcytosine (5mC). These C and G- five prime end carbon cytosine (C) bases that are adjacent to guanine (G) bases, resulting in five prime methylcytosine (5mC). These C and G rich regions are called CpG islands and are abundant in promoter regions.

DNA methylation can repress the expression of genes by blocking the promoter from its DNA transcription apparatus. DNA methylation is reversible; an enzyme called demethylase catalyzes the removal of methyl groups from cytosine.

Observation and determination of DNA methylation in a DNA sequence are performed using the bisulfite sequencing method. The sodium bisulfite (HSO₃^-) will react with cytosine (C) and turn it into uracil (U), whereas the 5-methylcytosine (5mC) will remain unaffected.

Figure 1. Sodium bisulfate conversion to differentiate methylated and unmethylated cytosine and comparison of reference (left) and bisulfite-treated DNA (right) sequence.

Methylation status can be determined using sequencing. Observed uracils correspond to unmethylated cytosines in the original sample, because DNA does not usually contain uracil. Cytosine bases that remain after bisulfite treatment are protected by methyl groups.

DNA methylation is part of gene regulation.