PUBLICATION
T-box binding sites are required for activity of a cardiac GATA-4 enhancer
- Authors
- Heicklen-Klein, A., and Evans, T.
- ID
- ZDB-PUB-050929-1
- Date
- 2004
- Source
- Developmental Biology 267(2): 490-504 (Journal)
- Registered Authors
- Evans, Todd
- Keywords
- Zebrafish, Transcriptional regulation, Valves, Transgenic, Heart development, T-box
- MeSH Terms
-
- Green Fluorescent Proteins
- GATA4 Transcription Factor
- Luminescent Proteins/metabolism
- Gene Components
- Blotting, Southern
- DNA-Binding Proteins/genetics*
- DNA-Binding Proteins/metabolism*
- Zebrafish
- Gene Expression Regulation, Developmental*
- Transcription Factors/genetics*
- Transcription Factors/metabolism*
- Heart/embryology*
- Mutagenesis, Site-Directed
- Promoter Regions, Genetic/genetics
- DNA Primers
- Animals, Genetically Modified
- Microinjections
- T-Box Domain Proteins/genetics
- T-Box Domain Proteins/metabolism*
- Animals
- In Situ Hybridization
- PubMed
- 15013808 Full text @ Dev. Biol.
Citation
Heicklen-Klein, A., and Evans, T. (2004) T-box binding sites are required for activity of a cardiac GATA-4 enhancer. Developmental Biology. 267(2):490-504.
Abstract
GATA-4 is a key regulator of a poorly understood cardiac morphogenetic program. We used genomic regions of the GATA-4 gene to target GFP expression to the developing heart of living fish. In these fish, GFP-expressing cells in the lateral plate mesoderm form two tubes that migrate ventrally to fuse into a linear heart tube. In addition, we find that a 14.8-kb fragment upstream of the transcription initiation site targets expression to both chambers and the valves of the heart. Truncation of 7 kb of the distal sequences eliminates expression in the atrium and the atrioventricular valve while expression is retained in the ventricle and the bulboventricular valve. Within this 7-kb distal regulatory region, we delineated a 1300-bp region with a cluster of consensus binding sites for T-box transcription factors. Mutation of these sequences significantly reduces reporter gene expression in the heart. This provides the first evidence that T-box factors function by directly regulating GATA-4 expression. Thus, GATA-4 regulatory elements control gene expression differentially along the rostro-caudal axis, and T-box binding elements in the GATA-4 promoter contribute to heart-specific expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping