DNA methyltransferases catalyze the transfer of the methyl group from S-andenosyl methionine (SAM) to DNA. Such methylation has wide ranging function in the cell, including organismal development and cell differentiation. In cancer, abnormal hypermethylation of gene promoter CpG islands can result in transcriptional silencing. De novo methyltransferases methylate unmethylated DNA, this occurs primarily during early embryonic development and sets the methylation pattern for that cell. Maintenance methyltransferases methylate hemimethylated DNA and continues the methylation pattern set during development. In mammals there are three DNA methyltranferases, DNMT1, DNMT3a and DNMT3b. All 3 are involved in DNA methylation during development, as well as coordinating the methlylation of histone thus participating in epigenetic regulation. However, each protein plays a slightly different role in the cell.
DNMT1 (DNA (cytosine-5-)-methyltransferase 1) is the most abundant maintenance methyltrasferase and it preferentially methylates hemimethylated CpG residues. It also maintains DNA methylation independent of replication by associating with chromatin during the G2 and M phases. Recent research suggests that SIRT1 can alter DNMT1 activity by deacylation of lysine residues. Deacylation of different lysines alter DNMT1 activity in different ways. (PMID: 21947282)
DNMT3a (DNA (cytosine-5-)-methyltransferase 3 alpha) is a de novo methyltransferase. It is capable of methlyating non-CpG sites. It may also preferentially methylate the DNA linker positioned between 2 nucleosomal cores and be inhibited by histone H1. It also plays a role in the imprinting. Point mutations at the DNMT3a homotetramer interface causes the formation of homodimers. These mutants show a loss of processivity characteristic of patients with AML. (PMID: 21979949)
DNMT3b (DNA (cytosine-5-)-methyltransferase 3 beta) may be involved in the methylation of the DNA in the nucleosome core region. By associating with CBX4 it acts as a transcriptional co-repressor. Together DNMT1 and DNMT2b are involved in the activation of the BAG1 gene by modulating the dimethlyation of the promoter histone H3 at the H3K4 and H3K9 residues. (PMID: 18413740).
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Good post!