Establishment and Maintenance of DNA Methylation

Abstract

In mammals, more than 70 % of the CpG sequences in the genome are methylated at the 5th position of cytosine bases. DNA methylation acts as a regulator of gene expression and is crucial for development, especially in higher eukaryotes. In mammals, three DNA (cytosine-5-)-methyltransferases, Dnmt1, Dnmt3a, and Dnmt3b, have been identified. Dnmt3a and Dnmt3b are mainly responsible for establishing DNA methylation patterns in the genome. For the establishment of DNA methylation patterns, interacting or associating factors that take Dnmt3a or Dnmt3b to the site of methylation, the timing of expression, and the substrate DNA with higher ordered structures (chromatin states) are the determinants. Dnmt1 favors methylation of hemi-methylated DNA, which appears just after replication or repair, and thus is responsible for maintaining the methylation patterns during replication and after repair. Recently, it was found that Uhrf1 and histone ubiquitylation are necessary factors for maintenance DNA methylation in vivo. In this chapter, the establishment and maintenance of DNA methylation by Dnmt3a, Dnmt3b, and Dnmt1 are described.