期刊
DEVELOPMENTAL BIOLOGY
卷 461, 期 2, 页码 124-131出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2020.02.001
关键词
Cardiac development; Transcription factor; Hey2; Ventricle; Enhancer; Tbx20
资金
- Japan Society for the Promotion of Science [15H04883, 15K15407, 16K08605, 18H02787, 19H03398, 19K17318]
- Takeda Science Foundation
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Miyata Cardiac Research Promotion Foundation
- Smoking Research Foundation
- Japan Agency for Medical Research and Development (AMED-CREST) [JP19gm0810001]
- Intramural Research Fund for Cardiovascular Diseases of National Cerebral and Cardiovascular Center
- Grants-in-Aid for Scientific Research [19H03398, 19K17318, 18H02787, 15K15407, 16K08605, 15H04883] Funding Source: KAKEN
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 a 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据