M. Frommer led the 1992 paper establishing a sequence-based display of 5-Methylcytosine in individual DNA strands. The method exploits the different responses of ordinary cytosine and methylated cytosine to bisulfite treatment: ordinary cytosine is preferentially converted to uracil, which is read as thymine after amplification, while methylated cytosine is relatively resistant.[ref]
This connects chemical modification to an ordinary sequence readout, making bisulfite sequencing a way to map DNA methylation. The untreated reference and conversion controls matter because an observed cytosine/thymine difference could otherwise be mistaken for a sequence variant or incomplete chemical conversion.
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