such as "Introduction", "Conclusion"..etc
There is growing
evidence revolving around ‘trio of events’ viz., human diseases, genetic
alternations and acquired epigenetic abnormalities. Much has been discussed in earlier sections
highlighting the significance of promoter CpG island methylation and gene
silencing. As shown by Harikrishnan et
al., (26) that the methylated DNA binding protein (MeCP2) is associated with
Brahma (Brm), a catalytic component
of SW1/SNF chromatin-remodeling complex.
Thus, it is clear that the cytosine methylation is mediated by
MeCP2. Further, there is a potential
link between cytosine methylation and chromatin silencing - one of the crux
events for the initiation of tumor and it is hypothesized to constitute a
distinct phenotype viz., ‘CpG island methylation phenotype’ (CIMP). Histone modification, such as, loss of
acetylation at lysine 16 and trimethylation at lysine 20 of histone H4 are the
epigenetic events prone to human cancer.
Besides, there is another interesting polycomb repressor complex (PRC 2)
in the initiation of genome silencing.
This contains histone methyltransferases which possibly translocate
methyl groups to lysine residues 9 and 27 of histone H3 (27). It is reported by Peter and Stephen (28) that
the polycomb gene (BMI1), a component of PRC1 is unusually over expressed in
several human cancers. In addition, transcription
of a number of tumor suppressor genes such as p16, BRCA1, p53, hMLH-1 has now
been shown to be inhibited due to the hypermethylation of their corresponding
promoter sites (29).
side of the coin in gene silencing is that the methylation of CpG dinucleotides
prevents transcription factors such as c-Myc
to recognize their foot-prints on DNA (30).
The above accumulated experimental evidences strongly indicate that the
entire methylated epigenome is customarily dysregulated causing cancer to
develop. These epigenetic dictums in
cancer have led to the development of an entirely new therapeutic approach in
which the focus is to reverse gene (tumor suppressor gene) silencing (28). Thus, the drugs inhibiting DNA methyl
transferase enzyme such as azanucleoside (31), 5-fluoro-2’-deoxycytidine (32)
and Zebularine (33) are under active consideration of FDA, USA
for treatment of cancer.
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