What is DNA methylation?
In addition to this flexible and dynamic module of the epigenome,
which is associated with the genome but is not part of its covalent structure,
the genome is covalently modified by addition of a methyl group at the 5th
position of the cytosine ring. Since the methyl group is connected to DNA
by a strong chemical bond, it is considered a stable and fixed mark. The vast
majority of methylated cytosines in vertebrate genomes are found in the dinucleotide
sequence CG. Not all CG dinucleotide sequences are methylated, different CGs
are methylated in different tissues creating a pattern of methylation that
is gene and tissue specific. Thus, there is a good correlation between the
state of activity of genes and lack of methylation of CGs in their regulatory
regions (Razin and Riggs, 1980). Remarkably, there is also a tight correlation
between the chromatin structure and the status of DNA methylation (Razin and
Cedar, 1977). We propose that the DNA methylation pattern is steady state
equilibrium of DNA methylation and demethylation reactions. DNA methylation
is catalyzed by DNA methyltransferase enzyme and demethylation catalyzed by
demethylase enzymes. The DNA methylation reaction is stimulated by inactive
chromatin and demethylation by active chromatin. Thus the direction of the
DNA methylation reaction is determined by chromatin structure.
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