Perspectives of FRET Imaging to Study Epigenetics and Mechanobiology in the Nucleus

Epigenetic modulations are crucial for the regulation of chromatin structures and genomic organizations, which are key factors determining gene expressions and cellular functions. Mechanical cues have also been shown to play important roles in modulating gene expressions and cellular functions. While there have been significant advances in our understanding of mechanotransduction in the nucleus, there is a lack of knowledge on the molecular details by which mechanical cues affect epigenetic and chromatin regulations to determine genetic outcomes. In this chapter we first introduce the current understanding on epigenetic regulations, particularly on histone modifications and DNA methylations. This is followed by the epigenetic regulations related to mechanobiology in the nucleus. We then introduce the development of genetically encoded molecular biosensors and the principles based on fluorescence proteins (FPs) and fluorescence resonance energy transfer (FRET) for the visualization of dynamic epigenetic regulations in single cells. Lastly, we present examples of the application of biosensors to visualize mechanotransduction events occurring in the nucleus in live cells. The single cell imaging of nuclear mechanotransduction can shed new lights on the molecular mechanisms regulating physiological and pathophysiological processes in living cells under different mechanical environments.