Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors

Dai Ihara, Yusuke Watanabe, Daiki Seya, Yuji Arai, Yoshie Isomoto, Atsushi Nakano, Atsushi Kubo, Toshihiko Ogura, Teruhisa Kawamura, Osamu Nakagawa

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Development of multi-chambered heart is associated with spatio-temporal regulation of gene expression. A basic helix-loop-helix transcription factor Hey2 is specifically expressed in the embryonic mouse ventricles and is indispensable for ventricular myocyte differentiation, compartment identity and morphogenesis of the heart. However, how Hey2 transcription is precisely regulated in the heart remains unclear. In this study, we identified a distal Hey2 enhancer conserved in the mouse and human to possess specific transcriptional activity in ventricular free wall myocytes at the looping stage of cardiac development. Deletion of the enhancer significantly decreased endogenous Hey2 expression in the ventricular myocardium but not in other tissues of mouse embryos. Mutation/deletion of the conserved binding sites for T-box and Gata proteins, but not NK-2 proteins, abolished the enhancer activity, and Tbx20 null mice completely lost the enhancer activity in the embryonic ventricles. Luciferase reporter analysis suggested that the ventricular enhancer activity was controlled by Tbx20 through its DNA binding and cooperative function with cardiac Gata proteins. These results delineate a regulatory mechanism of ventricular Hey2 expression and help fully understand molecular cascades in myocardial cell differentiation and cardiac morphogenesis during embryonic development.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalDevelopmental Biology
Volume461
Issue number2
DOIs
Publication statusPublished - 2020 May 15

Keywords

  • Cardiac development
  • Enhancer
  • Hey2
  • Tbx20
  • Transcription factor
  • Ventricle

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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