Liquid Chromatography Tandem Mass Spectrometry for the Measurement of Global DNA Methylation and Hydroxymethylation

DNA methylation is essential for normal development, cellular differentiation and tissue-specific gene expression [1]. In differentiated mammalian cells, DNA methylation occurs almost exclusively at cytosine bases located 5’ to a guanine, in a CpG dinucleotide. The distribution of DNA methylation across the genome is non-random. Most of the CpGs located in the genome are dispersed throughout the intergenic and intronic DNA regions such as repetitive DNA sequences where they are normally methylated to ensure DNA stability and transcriptional silencing of transposable elements [2]. In contrast, dense stretches of CpG dinucleotides found within the promoter regions of 70% of all genes (CpG islands) [3] are normally unmethylated.