DNA methylation dynamics at distal regulatory regions

While DNA methylation is well understood mechanistically, how it regulates and maintains cell fate and function is still largely unknown. High-resolution methylation maps, obtained from multiple tissues, established that the vast majority of tissue-specific Differentially Methylated Regions (DMRs) are located at distal, mostly noncoding, regulatory regions. Therefore, and in stark contrast to previous beliefs, the association between changes in DNA methylation and transcription levels is far from straightforward and the functional role of the majority of cell-specific DMRs remains to be determined.

To monitor real-time changes of DNA methylation in single living cells we have pioneered a novel reporter system that allows the identification and isolation of cells based on their methylation signature both in vitro and in vivo. The reporter system holds great promise for elucidating the functional roles of DNA methylation dynamics on cell fate and function with unprecedented resolution. Together with recent development of site-specific epigenetic editing tools, we are now able to functionally dissect causality relationships between DNA methylation changes and cellular phenotype