(789d) Engineering Recombinant Protein Sensors for Probing Epigenetic States in Live Cells

Epigenetics is a term that encompasses heritable changes in gene expression that do not change the underlying DNA sequence of the gene. Epigenetic modifications include chemical modifications such as methylation of DNA and acetylation, methylation or phosphorylation of histone protiens. These modifications play a key role in cellular processes such as differentiation. Aberrant changes in epigenetic modifications have been correlated with various types of cancers and neurological disorders. Current detection techniques of epigenetic changes require tedious sample pre-treatments and can be carried out only using a population of cells. Monitoring epigenetic changes in live cells will enable real-time characterization of cell response to various external factors such as environmental chemicals and drugs which are of primary importance to pharmaceutical industry and regulatory affairs agencies. Combined with state-of-the-art fluorescent techniques, we demonstrated the ability of our recombinant sensors in detecting epigenetic changes using both cellular extracts and in situ. The probe is compatible with live cell assays and can sensitively quantify the response of individual cells to drug treatments. The developed platform is ideal for monitoring in live cell changes in the epigenetic state and can be a extremly valuable tool for drug development and toxicology studies.