Ning Wang, PhDLeonard C. and Mary Lou Hoeft ProfessorUniversity of Illinois at Urbana-ChampaignHost: Professor Mark Johnson

Title:"Force-induced direct gene transcription in living cells"

Abstract:Despite decades of efforts, it remains elusive how physical forces influence gene expression in living cells and tissues. Here we show that gene transcription can be upregulated via force-induced direct chromatin stretching. Using green fluorescent protein (GFP) to label multiple sites in a chromatin domain and inserting a gene of interest between GFP spots, we were able to quantify the degree of chromatin stretching and transcription in a living cell. We found that transcription upregulation depended on force magnitude, force directionality, and the degree of chromatin stretching as well as tension in the cytoskeleton. Disrupting the force propagating pathway from the cytoplasm to the nuclear lamina abolished force-induced transcription. We discovered two nuclear proteins that transmitted force from nuclear lamins to the chromatin. We highlight our recent findings that forces and matrix mechanics regulate stem cell differentiation, early embryonic development, and growth and metastasis of malignant tumor-repopulating cells. Our findings demonstrate the critical roles of mechanotransduction in stem cell biology and cancer cell biology.