Stem Cell Models to Investigate the Role of DNA Methylation Machinery in Development of Neuropsychiatric Disorders

Figure 1

Specific roles of DNMTs in establishment and maintenance methylation in mammalian genomes. (a) Unmethylated DNA is acted upon by de novo methyltransferases DNMT3A and DNMT3B which methylated cytosines in the DNA molecule. The complementary strands are shown in green and red. This step also requires DNMT3L, the nonenzymatic member of DNMT family. (b) As a result of de novo methylation, methylated cytosines can be found in the context of both CpG and non-CpG dinucleotides. (c) After replication, the parental strand in each daughter DNA molecule serves as information for maintenance methylation. DNMT1 methylates cytosines in the daughter strand at positions that are exactly opposite to the methylated cytosines in the parent strand. (d) Because CpG dinucleotides are symmetric and exactly opposite in the daughter DNA, the maintenance methylation is highly efficient at CpG dinucleotides. Non-CpG dinucleotides do not contain cytosines at exactly the opposite positions in the two strands and therefore maintenance methylation in these dinucleotides is poor.