Cytoskeletal Protein Zyxin Inhibits the Activity of Genes Responsible for Embryonic Stem Cell Status

Zyxin is a cytoskeletal LIM domain protein that regulates actin cytoskeleton assembly and gene expression. In the present work, we found that Zyxin downregulation in Xenopus laevis embryos reduced the expression of numerous genes regulating cell differentiation but enhanced that of several genes responsible for embryonic stem cell status, specifically klf4, pou5f3.1, pou5f3.2 pou5f3.3 and vent2.1/2. For pou5f3 family genes (mammalian OCT4 orthologs), we showed that this effect was the result of mRNA stabilization due to complex formation with the Y-box protein Ybx1. When bound to Ybx1, Zyxin interfered with the formation of these complexes, thereby stimulating pou5f3 mRNAs degradation. In addition, in zebrafish embryos and human HEK293 cells, Zyxin downregulation increased the mRNA levels of the pluripotency genes KLF4, NANOG and OCT4. Our findings indicate that Zyxin may play a role as a switching hub coupling cell morphogenetic movements, differentiation and the embryonic stem cell status.