Saturday 11 January 2014




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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