Tbx20 controls the expression of the <i>KCNH2</i> gene and of hERG channels

Abstract

Significance Tbx20 is a transcription factor whose critical role in cardiogenesis is well-established. Here we functionally analyzed the electrophysiological effects produced by a mutation (p.R311C) in Tbx20 found in some affected individuals belonging to a family with long QT syndrome (an inherited cardiac arrhythmia due to delayed ventricular repolarization). We demonstrated that Tbx20 selectively increases the expression of KCNH2 , which encodes for the channel Kv11.1 (hERG) that generates the main ventricular repolarizing current. Conversely, the p.R311C mutation disables the Tbx20 protranscriptional activity over KCNH2 , leading to a decrease in the hERG current and a prolongation of the action potentials recorded in human induced pluripotent stem cell-derived cardiomyocytes. Therefore, we propose that Tbx20, besides its described role, regulates KCNH2 expression.