Biophysical Regulation of Epigenetic Reprogramming during TGFbeta1-Induced Epithelial-Mesenchymal Transition

Epithelial-mesenchymal transition (EMT) is a key developmental program that is co-opted in the progression of pathological conditions including fibrosis and cancer. During EMT, epithelial cells exhibit drastic morphological changes, alterations in gene expression patterns, and global epigenetic remodeling. We have previously demonstrated that biophysical signals regulate cell morphology and gene expression during EMT; however, the mechanisms governing epigenetic remodeling during EMT are not completely understood. Here, we employed microfabricated cell and tissue arrays to determine how biophysical cues modulate histone modifications during transforming growth factor (TGF)-β1-induced EMT. We find that matrix geometry regulates histone methylation and acetylation and we identify key factors governing the epigenetic reprogramming that occurs as a cell transitions from an epithelial to a mesenchymal phenotype. Results provide insight into how biophysical cues contribute to epigenetic remodeling and may suggest ways to regulate EMT related processes in the context of health and disease.