Mediators and dynamics of DNA methylation

As an inherited epigenetic marker occurring mainly on cytosines at CpG dinucleotides, DNA methylation occurs across many higher eukaryotic organisms. Looking at methylation patterns genome-wide classifies cell types uniquely and in several cases discriminates between healthy and cancerous cell types. DNA methylation can occur allele-specifically, which allows the cellular regulatory machinery to recognize each allele separately. Although only a small number of allele specifically methylated (ASM) regions are known, genome-wide experiments show that ASM is prevalent throughout the human genome. These DNA methylation patterns can be modified via DNA demethylation, which is important for induced pluripotent stem reprogramming and primordial germ cells. Recent evidence shows that the protein activation-induced cytidine deaminase plays a critical role in these demethylation events. Many transcription factors mediate DNA methylation patterns. Some transcription factors bind specifically to methylated or unmethylated sequences and other transcription factors protect genomic regions (e.g., promoter regions) from nearby DNA methylation encroachment. Possibly acting as another epigenetic regulatory layer, methylated cytosines are also converted to 5-hydroxyethylcyotines, which is a new modification type whose biological significance has yet been defined.