5-Methylcytosine is a methylated form of the DNA base cytosine (C) that regulates gene transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the expression of methylated genes can be altered (the study of this is part of the field of epigenetics). 5-Methylcytosine is incorporated in the nucleoside 5-methylcytidine. In 5-methylcytosine, a methyl group is attached to the 5th atom in the 6-atom ring, counting counterclockwise from the NH-bonded nitrogen at the six o'clock position. This methyl group distinguishes 5-methylcytosine from cytosine. While trying to isolate the bacterial toxin responsible for tuberculosis, W.G. Ruppel isolated a novel nucleic acid named tuberculinic acid in 1898 from Tubercle bacillus. The nucleic acid was found to be unusual, in that it contained in addition to thymine, guanine and cytosine, a methylated nucleotide. In 1925, Johnson and Coghill successfully detected a minor amount of a methylated cytosine derivative as a product of hydrolysis of tuberculinic acid with sulfuric acid. This report was severely criticized because their identification was based solely on the optical properties of the crystalline picrate, and other scientists failed to reproduce the same result. But its existence was ultimately proven in 1948, when Hotchkiss separated the nucleic acids of DNA from calf thymus using paper chromatography, by which he detected a unique methylated cytosine, quite distinct from conventional cytosine and uracil. After seven decades, it turned out that it is also a common feature in different RNA molecules, although the precise role is uncertain. 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).
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