The four bases that encode for genetic information in deoxyribonucleic acid (DNA) are commonly known as A, T G and C - adenine, thymine, guanine and cytosine respectively. However, apart from these four universally acknowledged bases, the fifth nucleotide, 5-methylcytosine (5-mC), has been revealed in the past decade. 5-methylcytosine is found to replace cytosine in DNA sequence and plays roles in gene regulation and expression. 5-methlycytosine formation is led by DNA methylation, catalysed by DNA methyltransferase which attaches methyl group to cytosine. It is believed that the discovery of the sixth DNA nucleotide will greatly excite the epigenetic field.
According to Skirmantas Kriaucionis, a postdoctoral associate in the Heintz lab, the sixth DNA nucleotide was found unintentionally in a 5-methlycytosine level investigation in large nuclei of Purkinje cells. Kriaucionis was intended to isolate the nuclei from different cells type and he noticed a significant amount of unexpected nucleotide. He further performed a series of test to indentify the strange nucleotide, including mass spectrometry, for a large number of trials and concluded that the unknown nucleotide is 5-hydroxymethlycytosine. Furthermore, it is a stable compound and is found abundantly in mouse and human brain. Yet, there are some studies conducted and have shown that 5-hydroxymethylcytosine can be found in simplest unicellular organisms DNA such as bacteriophage. The initial suggestion of 5-hydroxymethylcytosine role is in DNA methylation as well as in gene expressing regulation, as believed by Kriaucionis and Heintz.
The reason for the unrevealed of 5-hydroxymethylcytosine in genetics field is due to the methodologies used in most epigenetic experiments as it is only identified via bisulfate sequencing which is designed to identify DNA methylation site, say Kriaucionis and Heintz. It is deduced that 5-hydroxymethylcytosine is arise from 5-methylcytosine conversion, based on a paper published in Science by an independent group at Harvard.
Kraiucionis is then paying effort in studying the effects of over- or underexpress of 5-hydroxymethlycytosince via genetically modify mice. Apart from that, the discovery of this new nucleotide is believed to draw massive attention in epigenetic, genetic and of course, biology fields; thus results in more findings and discoveries and unmask of the mysteries.
Ai Ngor Chew
41876646
Original article:
Brett Norman (2009). New nucleotide could revolutionize epigenetics.
Accessed from: http://www.bio-medicine.org/biology-news-1/New-nucleotide-could-revolutionize-epigenetics-8009-4/
Image from:
http://commons.wikimedia.org/wiki/File:MGMT%2BDNA_1T38.png
