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Expression of Hey2 transcription factor in the early embryonic ventricles is controlled through a distal enhancer by Tbx20 and Gata transcription factors
- Source :
- Developmental Biology. 461:124-131
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
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.
- Subjects :
- TBX20
Heart Ventricles
Morphogenesis
Mice, Transgenic
Biology
Mice
03 medical and health sciences
0302 clinical medicine
Species Specificity
Genes, Reporter
Transcription (biology)
Sequence Homology, Nucleic Acid
Basic Helix-Loop-Helix Transcription Factors
Animals
Humans
HEY2
Enhancer
Molecular Biology
Transcription factor
Conserved Sequence
Sequence Deletion
030304 developmental biology
Mammals
Regulation of gene expression
0303 health sciences
Base Sequence
Gene Expression Regulation, Developmental
Cell Biology
GATA4 Transcription Factor
Cell biology
Repressor Proteins
Enhancer Elements, Genetic
cardiovascular system
GATA transcription factor
T-Box Domain Proteins
Sequence Alignment
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 00121606
- Volume :
- 461
- Database :
- OpenAIRE
- Journal :
- Developmental Biology
- Accession number :
- edsair.doi.dedup.....f922f78fcc096ef8b182968e3f5a7f9e