The DNA methyltransferases are a family of enzymes that add a methyl group (-CH3) to DNA in a process called methylation (for a 3D structure of the enzyme click here). DNA methylation is considered to be an epigenetic change because it does not alter the actual genetic sequence. DNA methyltransferase specifically modifies the nucleotide cytosine to methylcytosine when it occurs in a CpG island. A CpG island is a string of cytosines (C) and guanines (G) (“p” stands for the phosphate between the two nucleotides where they bind to one another on the backbone). Thus, the genetic sequence can have blocks of methylation, though variations in the pattern are seen, and the exact reason for this is not known.
Current understanding is that the presence of the methyl groups on the DNA results in heterochromatin, a tertiary structure of DNA tightly wound around protein structures called histones. This configuration makes it difficult for transcription factors to come into contact with the DNA, essentially turning genes off by preventing their transcription, the first step in gene expression. Some specific factors preferentially bind methylcytosine, possibly influencing gene expression.
DNA methylation patterns are not identical in everyone. Recent studies found that the DNA sequence and epigenome are inherited independently of one another, which may explain differences in identical twins. In humans, three DNA methyltransferases are responsible for creating and maintaining the methylation pattern: DNMT1, DNMT3a, and DNMT3b. Deficiencies in just one of these enzymes can result in immunodeficiency and disease. This implies an indispensable role of methylation, and this enzyme, in gene expression and human health (Jin et al. 2008).
Specific Processes Involving DNA Methyltransferase
– Altered methylation patterns are thought to play a role in the development of some cancers, which tend to result from increased or aberrant gene expression, as well as problems with cell division (Milutinovic et al. 2004).
-DNA methyltransferase plays a role in imprinting, the process by which sections of chromosomes are turned off in an organism based on inheritance. This is seen in some chromosomal duplications, preventing illness and/or lethality from the expression of more alleles than usual.
-Because of the high level of replication and gene expression needed during embryonic development, DNA methylation is virtually absent during that stage. However, DNA methyltransferase is still a necessary enzyme. As cells differentiate, genes start to get shut off to eliminate unnecessary proteins (see EpiDNA).
-Methylcytosine binding factors may influence advancement through the cell cycle (Squillaro et al. 2010).
