1. Signaling Pathways
  2. Epigenetics
  3. DNA Methylation

DNA Methylation

DNA methylation is a common epigenetic alteration and considered a heterochromatin mark. DNA methylation plays an important role in maintaining the stability of genome, genomic imprinting, inactivation of X-chromosome in females, regulation of transcription and also in the developmental process of an organism.

DNA methylation modifications include 5-methylcytosine (5mC), N6-methylladenine (6mA) and 4-methylcytosine (4mC). Among them, 6mA and 4mC are prevalent in prokaryotic genomes, 5mC is the most widely distributed type of methylation in eukaryotes. DNA methyltransfer¬ases (DNMTs) target CpG sites and actively methylate DNA. DNMT3A/B are the “de novo” DNMTs and transfer methyl groups onto naked DNA. However DNMT1 preserves preexisting pattern of methylation after cell replication. DNA methylation is recognized by three separate families of proteins: the MBD (methyl-CpG-binding domain) proteins, the UHRF (ubiquitin-like, containing PHD and RING finger domain) proteins, and the zinc-finger proteins.

DNA demethylation is characterized as either passive or active. The inhibition or dysfunction of DNMTs allows newly incorporated cytosine to remain unmethylated and consequently reduces the overall methylation level following each cell division. Active DNA demethylation requires enzymes (such as activation-induced cytidine deaminase (AID) and 10 to 11 translocation (TET) enzymes) to process the 5mC in order to revert it back to a naked cytosine.