ZFIN ID: ZDB-PUB-090330-13
Transient and transgenic analysis of the zebrafish ventricular myosin heavy chain (vmhc) promoter: An inhibitory mechanism of ventricle-specific gene expression
Zhang, R., and Xu, X.
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.
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.