DNA methylation

Phenomenon

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FIG. 1.   Methylation of cytosine residues in the mammalian genome. (A) Structure of the cytosine residue and its methylated derivative, 5-methylcytosine, which is methylated at the 5 position of the carbon ring of the cytosine residue. The structure of the thymine residue is also shown, to illustrate that mutational deamination at the 4 position of 5-methylcytosine results in thymine. (B) After replication, daughter strands of fully methylated DNA are hemimethylated (reaction 3) and the original pattern of DNA methylation is maintained by the DNA methyltransferase (reaction 2), which preferentially methylates the cytosine residues at hemimethylated CpG sites. Further replication without methylation of the hemimethylated DNA results in fully unmethylated DNA (reaction 4). De novo methylation (reaction 1) is also considered to be mediated by the DNA methyltransferase, although the efficiency of de novo methylation is low. This figure was taken from Goto and Monk, 1998.

Method to detect methylation

  1. Principle: some restriction enzyme will not cut methylated DNA, such as HpaII (CCmGG)
  2. Control: Many restriction enzymes have isoschizomer, e.g. the isoschizomer of the above enzyme, MspI, can cut (CCmGG)

Reference

Tetsuya Goto* and Marilyn Monk (1998) Regulation of X-Chromosome Inactivation in Development in Mice and Humans. Microbiol Mol Biol Rev. 62, 362-378