Profiling of epigenetic DNA modifications by advanced liquid chromatography-mass spectrometry technologies

Abstract Four DNA bases are essential biochemical elements for coding heritable life blueprint. Meanwhile, organisms utilize modifying enzymes to post chemical groups on DNA bases to regulate gene expression, chromosome structures, and transposase activity, and to defense pathogens. The researches on the biochemical modifications of DNA bases are at the cutting edge of life sciences and chemical biology. Up to date, along with fantastic progresses, liquid chromatography hyphenated with mass spectrometry (LC-MS)-based technologies become popular and powerful tools for chemical structure-dependent identification and quantification of diverse DNA modifications. Here we provided comprehensive review on LC-MS-based technologies and related pretreatment technologies for profiling of epigenetic DNA modifications, mainly focusing on innovative technologies developed for desalting, DNA digestion, and ionization for mass spectrometry detection. We also summarized the epigenetic progresses, which benefited from the development of the LC-MS methodologies and technologies, on the studies of specific DNA modifications, in particular, 5-hydroxymethylcytosine and 5-formylcytosine.