(466a) Matrix Rigidity Modulates Histone H3 Modifications during Epithelial-Mesenchymal Transition

Epithelial-Mesenchymal Transition (EMT) is a physiological process that is essential during embryogenesis and wound healing and is also a contributor to pathologies including fibrosis and cancer. EMT is promoted by increased extracellular matrix stiffness and is characterized by loss of epithelial markers such as E-cadherin and gain of mesenchymal traits such as increased expression of cytoskeletal proteins and enhanced cell motility. In addition, epigenetic reprogramming, including histone modifications, change chromatin structure and regulate gene transcription during EMT; however, there is limited knowledge available on how mechanical signals control epigenetic remodelling in the context of EMT. Here, we synthesized hydrogels with mechanical properties that span that of normal and diseased mammary tissue and examined the response of mammary epithelial cells to transforming growth factor (TGF)β1-induced EMT. Using immunofluorescence staining and western blotting, we found that matrix stiffness and TGFβ1 together regulate acetylation and methylation patterns of histone H3 that are associated with transcriptional activation and silencing. Furthermore, treatment with contractility inhibitors modulated the levels of histone marks in response to EMT induction cues. Thus, matrix rigidity may regulate EMT process in part through control of epigenetic modifications and gene transcription. These findings may suggest strategies to improve tissue engineering approaches and ways to prevent EMT in pathological processes such as cancer.