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Biology Articles » Genetics » Epigenetic Microenvironment Awakes Genes » Methylation of CpG Islands

Methylation of CpG Islands
- Epigenetic Microenvironment Awakes Genes

 CpG dinucleotides are found in clusters and thus constitute CpG islands.  In vertebrates, 60 to 90% of all CpGs are methylated.  The remaining non-methylated CpGs  include functional promoters in the region more towards 5’ end (20).  They are found to contain highly acetylated histones, H3 and H4.  There are regions of which each is greater than 200 bp with high GC content (>0.6).  Methylation of cytosines at the carbon 5’ position of CpG dinucleotides is a characteristic feature of many eukaryotic genomes (13).  The salient property of CpG Island is that it is unmethylated in the germ line. It is suggested that CpG island methylation has a dominant effect upon comparison with histone deacetylation in silencing genes (13).  The lactoferrin promoter that resides immediately upstream from the estrogen response element contains 5 CpG sites within the region from 590 to 330 bp (21).  Further, it is reported that CpG island in the estrogen receptor gene is hypermethylated in human breast cancer cells and also in sporadic colorectal tumerogenesis. Mujumder, et al., (22) have shown that Metallothionein 1 gene is silenced by methylation of CpG islands present within 216 bp to +1 bp with respect to transcription start in mouse lymphosarcoma P 1798 cells. Furthermore, the intriguing feature is that there is an association between the promoter regions of many tumor suppressor genes and de novo  methylation of an entire CpG island (23)  which is the primary cause for the genesis of tumor.

 

There is a family of highly conserved proteins namely methyl CpG binding proteins sharing a common binding domain (MBD family) selectively docks to methylated CpG dinucleotides. Huck and Adrain (13) indicated that the transcriptional silencing is also mediated by methyl CpG binding protein (MeCP2) which is found to interact with Sin3/ histone deacetylase co-repressor complex.  Thus,  methylation of CpG island results in the alteration of chromatin structure followed by the direct impediment in the binding of  positive factors  to the regulatory elements (15) and ultimately rendering the sites inaccessible to the basal transcriptional machinery i.e., prevention of interaction of transcription factors with the promoters.


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