DNA METHYLATION AND EPIGENETIC GENE SILENCING

DNA  METHYLATION AND EPIGENETIC GENE SILENCING

 

     DNA methylation is a reversible chemical modification of the cytosine in the CpG islands  of promoter sequences, catalyzed by a family of DNA methyltransferases. DNA  methylation does not change  the genetic information but it just alters the readability of the DNA  and results  in the  inactivation of gene by  subsequent transcript repression.  CpG island  are the regions  in DNA  that  contains  many adjacent cytosine and guanine nucleotides. The ''p '' in CpG  refers to the phosphodiester bond between  the cytosine   and  the guanine. These islands  occur  in  approximately  40% of the promoters  of human  genes. These 

islands occur  in approximately 40%  of the promoters  of human genes. DNA methylation  plays  a critical  role in the control  of cellular  process  including  embryonic development , transcription, X- chromosome inactivation and  genomic imprinting. DNA  methylation occurs in the C5 positions of cytosines that precedes guanines and  are called dinucleotide CpGs. The CpG dinucleotides are not found frequently throughout the human genome and present 20 % of its  expected frequency. But approximately half of the human gene promoter regions have CpG rich areas of 0.5 to 2 kb in length. In which CpG dinucleotide frequency are higher than expected . These CpG rich areas are often known  as CpG islands. . The majority (94%) of CpG island  remain  unmethylated  in normal cell. But particular subgroups of promoters CpG are  methylated  such as tissue  and germ line specific genes. In general , CpG  island methylation causes gene silencing. The  methylated CpG  island  also recruit   histone deacetylases  and other factor involved  in

transcriptional silencing .  In activation  of tumor suppressor genes through  hypermethylation of CpG islands within promoters regions is a major event in carcinogenesis. Hypermethylation of CpG

  islands within promoter regions  is a major  event in  carcinogenesis . Hypermethylation of CpG  island also has silencing effect on miRNA  in cancer. Micro RNA are short , 18-22  nucleotide, noncoding RNas that regulate many cellular functions including cell proliferation, apoptosis and differentiation by silencing specific target  genes through translational repression or mrNa degradation.