Zeb1 Is a Key Regulator of Cardiomyocyte Structure and Function

We identified Zeb1 as a downstream target of the RNA-binding protein CPEB4 in cardiac hypertrophy. While Zeb1's role in cancer and EMT is well known, its impact on cardiomyocytes remains largely underexplored. We hypothesize that Zeb1 regulates cardiomyocyte maturation and function, which is crucial for structural integrity and contractility. Zeb1 deletion disrupts sarcomeric organization and induces cardiac dysfunction, notably more severe in females. RNA sequencing confirms that Zeb1 loss in females increases the expression of epithelial and Extracellular Matrix (ECM) genes. Zeb1's overexpression induces pathological hypertrophy and progressive cardiac dysfunction.