The main goal of our research is to integrate different cutting-edge technologies, including FRET, molecular engineering, live cell imaging, chromatin labeling and biomechanics, to develop epigenetic FRET biosensors in order to address fundamental biological/ physiological questions, e.g. epigenetic regulation and mechano-transduction, not only in global but also at specific genomic loci. It is apparent that the posing and answering of these fundamental questions lie beyond the capability of traditional biochemical approaches. Our research can advance our systematic and in-depth understanding of how cells coordinate epigenetic modifications in response to physical and chemical environmental cues.