DNA methylation is a post-replicative process. The extention of the modifications regarding the DNA methylation is basically determined during development. DNA methylation is therefore one of the mechanisms related with cell differentiation through inhibition of gene expression at the transcriptional level and is essential for the normal development of mammals, it is associated with genomic imprinting, transcriptional inactivation of the X chromosome and aging, has a role in the development of pathological events, such as cancerogenesis.
DNA methylation is an epigenetic post-synthetic modification that, with the transfer of a methyl group from S- adenosylmetionina C atom in position 5 of the cytosine ring, introduces 5mC as the new base in the DNA.
The CpG islands contain CpG dinucleotides at a frequency mathematically predetermined. The CpG islands are about 30,000 generally located 5 'end of the promoter region of housekeeping genes, sometimes overlapping the region coding for a variable extension (usually the first exon). The frequency of the presence the CpG dinucleotides in the genome is less than expected, except for the regions of CpG islands. This is the result of an evolutionary mechanism linked to the presence of a spontaneous deaminase activity in the nucleus. This enzymatic reaction transforms the methylated cytosine in thymine and the non-methylated C in Uracil. Checks and repair mechanisms recognize the Uracil base as extraneous DNA and therefore replace, while this substitution does not occur for Thymine, common base in the DNA. The most CpG are no methylated in a normal cell, regardless of the state of the transcriptional gene, while during cancer development the CpGs outside of CpG islands become ipometilated, and CpG islands in the promoter region of tumor suppressor genes become hypermethylated. This hypermethylation is associated with chromatin condensation and loss of transcription.The most recent data indicate that genetic and epigenetic events interact to help the progressive development of the cancers.
