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ABSTRACT Extracellular matrix stiffness is enhanced in cancer and fibrosis; however, there is limited knowledge on how matrix mechanics modulate expression and signaling of the methyltransferase G9a. Here, we show that matrix stiffness and transforming growth factor (TGF)‐β1 signaling together regulate G9a expression and the levels of the histone mark H3K9me2. Suppressing the activity and expression of G9a attenuates TGFβ1‐induced alpha smooth muscle actin (αSMA) and N‐cadherin expression and cell morphology changes in mammary epithelial cells cultured on stiff substrata. Knockdown of G9a increases the expression of large tumor suppressor kinase 2 (LATS2) and decreases the nuclear localization of yes associated protein (YAP). Furthermore, inhibition of LATS promotes an increase in YAP nuclear localization and αSMA expression, while inhibition of YAP attenuates αSMA expression. Overall, our findings indicate that a G9a‐LATS‐YAP signaling cascade regulates mammary epithelial cell response to matrix stiffness and TGFβ1. 

ABSTRACT The methyltransferase enhancer of zeste homolog 2 (EZH2) regulates gene expression, and aberrant EZH2 expression and signaling can drive fibrosis and cancer. However, it is not clear how chemical and mechanical signals are integrated to regulate EZH2 and gene expression. We show that culture of cells on stiff matrices in concert with transforming growth factor (TGF)-β1 promotes nuclear localization of EZH2 and an increase in the levels of the corresponding histone modification, H3K27me3, thereby regulating gene expression. EZH2 activity and expression are required for TGFβ1- and stiffness-induced increases in H3K27me3 levels as well as for morphological and gene expression changes associated with epithelial–mesenchymal transition (EMT). Inhibition of Rho associated kinase (ROCK) proteins or myosin II signaling attenuates TGFβ1-induced nuclear localization of EZH2 and decreases H3K27me3 levels in cells cultured on stiff substrata, suggesting that cellular contractility, in concert with a major cancer signaling regulator TGFβ1, modulates EZH2 subcellular localization. These findings provide a contractility-dependent mechanism by which matrix stiffness and TGFβ1 together mediate EZH2 signaling to promote EMT. 

This article describes the development of polymer brush-based heterogeneous photocatalysts for PET-RAFT polymerization in aqueous environments. 

Finned hierarchical MOF particles (Cu(BDC) nanosheets as fins grown perpendicularly on Ni 2 (BDC) 2 (DABCO) hexagonal prisms) were synthesized on modified cellulose support. The hierarchical MOF particles exposed the open Cu( ii ) sites on Cu(BDC) to enable selective 1-hexene/ n -hexane separation.