5-Methylcytosine - in Vivo

In Vivo

5-Methylcytosine is an epigenetic modification formed by the action of DNA methyltransferases.

The function of this chemical varies significantly among species:

• In bacteria, 5-methylcytosine can be found at a variety of sites, and is often used as a marker to protect DNA from being cut by native methylation-sensitive restriction enzymes.
• In plants, 5-methylcytosine occurs at CpG, CpHpG and CpHpH sequences (where H = A, C or T).
• In fungi and animals, 5-methylcytosine predominantly occurs at CpG dinucleotides. Most eukaryotes methylate only a small percentage of these sites, but 70-80% of CpG cytosines are methylated in vertebrates.

While spontaneous deamination of cytosine forms uracil, which is recognized and removed by DNA repair enzymes, deamination of 5-methylcytosine forms thymine. This conversion of a DNA base from cytosine (C) to thymine (T) can result in a transition mutation. In addition, active enzymatic deamination of cytosine or 5-methylcytosine by the APOBEC family of cytosine deaminases could have beneficial implications on various cellular processes as well as on organismal evolution. The implications of deamination on 5-hydroxymethylcytosine, on the other hand, remains less understood.

In a NIH-funded study (profiled by Marjorie Montemayor-Quellenberg on the Harvard Gazette's website, and published on Friday, September 14, 2012, in "Cell") conducted by teams of researchers in Boston, Massachusetts at Harvard University Medical School (HMS), and one of its affiliates, Brigham and Women's Hospital (BWH), led by HMS Assistant Professor of Medicine, Dr. Yujiang Geno Shi, Ph.D., and Dr. George F. Murray, M.D., of BWH's Department of Pathology, it was found that "loss of ... 5-hmC in skin cells serves as a key indicator for malignant melanoma. Loss corresponded to more-advanced stages of melanoma as well as clinical outcome... Strikingly, researchers were able to reverse melanoma growth in preclinical studies. ...".