Fig. 1

DNA methylation dynamics and human phenotypic variations. a In humans, three different DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) are responsible for methylating the genomic DNA (primary substrate) at the 5’ position of the cytosine residue. The methyl group donor is S-adenosyl-L-methionine (SAM, also called cofactor or secondary substrate) which is oxidized to S-adenosyl-L-homocysteine (SAH) after donating the methyl group. In the genome, the methyl groups of cytosine residues are removed by ten-eleven translocation proteins (TET1, TET2, TET3) which use Fe²⁺ and ascorbate as additional cofactors. In a separate reaction system inside the cells, SAH is reduced to methionine using cofactor 5-methyl-tetrahydrofolate (MTHF), and the methionine is converted back to universal methyl donor SAM using an ATP molecule. b DNA methylation profile of human tissues/cells is affected by its immediate environment and activities such as lifestyle, eating habits, alcoholism, smoking, diseased, aggressive, drug addiction, perpetual criminal commitment, etc. The combined effect of the geographical location and the personal experiences/behaviors of individuals which are usually repetitive in nature leave behind certain methylation marks on their DNA