DNA methylation
DNA methylation changes the interactions between proteins and DNA, which can lead to alterations in chromatin structure and either a decrease or an increase in the rate of transcription (Jones, Takai 2001). All healthy cells contain DNA, which, to some degree, is methylated.
Hypermethylation is an increase in the
number of methyl groups on the DNA strand and is often linked to gene mutations
and gene silencing. Hypomethylation is a decrease in the amount of the
methylated DNA and is linked to DNA instability and activation of genes that
are normally silenced, such as oncogenes in cancer cells (Clark and Melki,
2002). Methylation is a regulatory mechanism involved in both initiation of
transcription and silencing of genes, depending on the type of methylation and
the gene that is methylated (Tost, 2008).
Fig. The
methylation takes place on the 5-carbon in cytosine (Laboratory 2007).
Repression caused by DNA methylation can
happen directly or elaborately. The direct way is when the methyl groups
inhibit the transcription factors from binding to the promoter region. The
elaborate way represses DNA expression with the use of other chromatin
modifying factors, which bind to methylated CpGs (Bogdanovic and Veenstra,
2009). CpG is an abbreviation for cytosine and guanine separated by a phophate
and is derived from the way they are connected in the DNA strands (Allis,
2007).
DNA Demethylation
The demethylation takes place in several
steps. First the methylated cytosine residue has an oxidative deamination,
meaning that the amine of the 4-position carbon is changed to oxygen, and
thereby the methylated cytosine becomes a thymine.(Ooi, Bestor 2008).
The deamination gives a T/G mismatch
basepair, which can be restored by the DNA repair system by removal of the
thymine. Then the base excision repair system inserts an unmethylated cytosine,
thus ending with an unmethylated C/G basepair (Ooi, Bestor, 2008). The demethylation
process is, surprisingly, thought to be initiated by the DNMT3a and DNMT3b,
which are normally associated with the DNA methylation (Gehring, Reik et al.,
2009). This suggests that DNMT3a and DNMT3b are involved in demethylation and
methylation, which both are important mechanisms during gene transcription.
Absence of the methyl donor SAM seems to favour the conversion of methylated
cytosine to thymine (Ooi and Bestor, 2008).
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