Substrate rigidity-dependent positive feedback regulation between YAP and ROCK2

Abstract

<p>Extracellular matrix (ECM) stiffness influences gene expression, leading to modulation of various cellular functions. While ROCK2 regulates actomyosin activity as well as cell migration and proliferation, expression of ROCK2 is increased in response to stiffening ECM. However, the mechanism underlying rigidity-dependent <i>ROCK2</i> expression remains elusive. Here, we show that YAP, a mechanically regulated transcription coactivator, upregulates <i>ROCK2</i> expression in an ECM rigidity-dependent manner. YAP interacted with the <i>ROCK2</i> promoter region in an actomyosin activity-dependent manner. Knockdown of <i>YAP</i> decreased <i>ROCK2</i> expression while activity of the <i>ROCK2</i> promoter was upregulated by expressing constitutively active YAP. Furthermore, we found that <i>ROCK2</i> expression promotes transcriptional activation by YAP. Our results reveal a novel positive feedback loop between YAP and ROCK2, which is modulated by ECM stiffness.</p