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The contribution of mass spectrometry to the epigenetics field is owing to its powerful sequencing capacity that helped identify dozens of new modification sites and types and expand the knowledge of the locations of modifications previously discovered by Edman degradation at the N-terminus and C-terminus to the whole protein sequence. Normally, proteins are first cut by a protease, such as trypsin, into mass spectrometry-favorable peptides and then the nature of modification at a specific site, together with the peptide sequence, is unambiguously determined by mass spectrometry. Mass spectrometry with a scan mode of selective ion monitoring (SIM) or selective and multiple reaction monitoring (SRM and MRM) may be the method of choice for quantification of epigenetic modifications with unmatched sensitivity and selectivity.
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