PUBLICATION
Transient and transgenic analysis of the zebrafish ventricular myosin heavy chain (vmhc) promoter: An inhibitory mechanism of ventricle-specific gene expression
- Authors
- Zhang, R., and Xu, X.
- ID
- ZDB-PUB-090330-13
- Date
- 2009
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 238(6): 1564-1573 (Journal)
- Registered Authors
- Xu, Xiaolei, Zhang, Ruilin
- Keywords
- Vmhc, chamber specificity, promoter analysis, transgenic fish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Gene Expression Regulation, Developmental*
- Heart Ventricles/embryology*
- Heart Ventricles/metabolism
- Myosin Heavy Chains/genetics*
- Myosin Heavy Chains/metabolism
- Promoter Regions, Genetic*
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Zebrafish*/anatomy & histology
- Zebrafish*/embryology
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 19322764 Full text @ Dev. Dyn.
Citation
Zhang, R., and Xu, X. (2009) Transient and transgenic analysis of the zebrafish ventricular myosin heavy chain (vmhc) promoter: An inhibitory mechanism of ventricle-specific gene expression. Developmental Dynamics : an official publication of the American Association of Anatomists. 238(6):1564-1573.
Abstract
The zebrafish ventricular myosin heavy chain (vmhc) gene exhibits restricted expression in the ventricle. However, the molecular mechanism underlying this chamber-specific expression is unclear. Here, we exploited both transient and transgenic technologies to dissect the zebrafish vmhc promoter. We demonstrated that a combination of two transient assays in this animal model quickly identified chamber-specific cis-elements, isolating a 2.2 kb fragment upstream from the vmhc gene that can drive ventricle-specific expression. Furthermore, deletion analysis identified multiple cis-elements that exhibited cardiac-specific expression. To achieve chamber specificity, a distal element was required to coordinate with and suppress a proximal enhancer element. Finally, we discovered that Nkx2.5-binding sites (NKE) were essential for this repressive function. In summary, our study of the zebrafish vmhc promoter suggests that ventricle-specific expression is achieved through an inhibitory mechanism that suppresses expression in the atrium. Developmental Dynamics, 2009. (c) 2009 Wiley-Liss, Inc.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping