Aberrations in DNA methylation are linked to numerous diseases including imprinting disorders (such as Prader-Willi and Angelman syndromes), neurodegenerative syndromes and repeat sequence instability. Furthermore, multiple lines of evidence have indicated that changes in methylation are correlated with different stages of tumor progression and metastasis in various cancers. However, without means of monitoring real-time epigenetic changes or tools to directly modify the epigenome, it is highly challenging to dissect the functional contribution of specific DNA methylation changes to disease pathogenesis.
Our approach may be broadly adapted to other dynamic systems, opening new avenues for elucidating the contribution of DNA methylation dynamics to cell fate decisions in disease and cancer. Attractively, establishing a traceable readout of locus-specific methylation changes may facilitate screening for factors to revert the epigenetic phenotype.