Environmental Regulation of the Estrogen Response in Single Cells

Gene regulation is complex, involving the coordination of hundreds of proteins, including chromatin remodelers, enhancer RNA and chromosome looping. The estrogen response has served as a model of gene regulation due in part to its rapid and extensive induction. Single molecule RNA imaging in living cells has shown that this process is dynamic and heterogenous in time leading to differences in cell responsiveness and expression in the cell population. This variability in expression at the tissue and single cell level increases with age, implicating environmental epigenetic regulation. Environmental factors such as endocrine disruptor chemicals are found in our food and can disrupt the normal estrogen response. However, how single cells respond to endocrine disruptor chemicals is unclear. To investigate the interplay between the environment and the estrogen response we are using single-molecule imaging of the estrogen receptor and transcription in living cells. This work will reveal mechanistic insights into how environmental factors perturb estrogen receptor mediated transcription.