Novel Tools to Map DNA and RNA Epigenetic Footprints Nucleic acids, which include DNA and RNA (the DNA “message” transmitter), carry the genetic information that encodes the building blocks of cells and tissues. Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry and Howard Hughes Investigator, and colleagues study how specific modifications, such as methylation, to RNA can lead to changes in how genes are expressed and, ultimately, result in disease. This field is referred to as epitranscriptomics. He is truly a pioneer of the field. In 2011, his laboratory discovered the first RNA demethylase, an “eraser” enzyme that removes methyla- tion modifications, and went on to show for the first time that it is possible to reverse RNA modifica- tions. His team has also identified “reader” proteins that specifically bind and affect methylated RNA in mammalian cells and “writers” that are responsible for methylat- ing RNA. At the center of much of this research is innovative technology— new methodologies to map and capture DNA and RNA modifica- tions using sophisticated chemis- try approaches. For example, He recognized that the lack of tech- niques to distinguish one DNA modification (5–hydroxymethylcy- tosine) from another (5–methylcy- tosine) limited scientists’ ability to understand the role of these modifications in cancer and other diseases. Therefore, his team developed the first chemical labeling approach to isolate 5–hmc–enriched DNA, and subsequently improved the resolution (i.e., the amount of detail detectable) to single DNA bases. More recently, He’s labora- tory developed a highly sensitive and selective chemical labeling and capture approach for genome– wide profiling of 5hmC with a very small sample size (approximately 1,000 cells). These new tools have allowed He and his collaborators to gener- ate detailed epigenetic footprints that were not possible previously. He’s team is characterizing such modifications in a wide array of 10 Powered by Innovation