GATA-4 and MEF2C transcription factors control the tissue-specific expression of the alphaT-catenin gene CTNNA3

AlphaT-catenin is a recently identified member of the alpha-catenin family of cell-cell adhesion molecules. Its expression is restricted mainly to cardiomyocytes, although it is also expressed in skeletal muscle, testis and brain. Like other alpha-catenins, alphaT-catenin provides an indispensable l...

Full description

Saved in:
Bibliographic Details
Published in:Nucleic acids research 2004, Vol.32 (14), p.4155-4165
Main Authors: Vanpoucke, Griet, Goossens, Steven, De Craene, Bram, Gilbert, Barbara, van Roy, Frans, Berx, Geert
Format: Article
Language:English
Subjects:
alpha Catenin
Animals
Base Sequence
Binding Sites
Cell Line
Cytoskeletal Proteins - biosynthesis
Cytoskeletal Proteins - genetics
DNA-Binding Proteins - physiology
GATA4 Transcription Factor
Humans
MADS Domain Proteins
MEF2 Transcription Factors
Mice
Mice, Transgenic
Molecular Sequence Data
Myocytes, Cardiac - metabolism
Myogenic Regulatory Factors - physiology
Organ Specificity
Promoter Regions, Genetic
Regulatory Sequences, Nucleic Acid
Sequence Alignment
Transcription Factors - physiology
Transcriptional Activation
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:AlphaT-catenin is a recently identified member of the alpha-catenin family of cell-cell adhesion molecules. Its expression is restricted mainly to cardiomyocytes, although it is also expressed in skeletal muscle, testis and brain. Like other alpha-catenins, alphaT-catenin provides an indispensable link between a cadherin-based adhesion complex and the actin cytoskeleton, resulting in strong cell-cell adhesion. We show here that the tissue-specificity of alphaT-catenin expression is controlled by its promoter region. By in silico analysis, we found that the alphaT-catenin promoter contains several binding sites for cardiac and muscle-specific transcription factors. By co-transfection studies in P19 embryonal carcinoma cells, we demonstrated that MEF2C and GATA-4 each have an activating effect on the alphaT-catenin promoter. Transfections with wild-type and mutant promoter constructs in cardiac HL-1 cells indicated that one GATA box is absolutely required for high alphaT-catenin promoter activity in these cells. Furthermore, we showed that the GATA-4 transcription factor specifically binds and activates the alphaT-catenin promoter in vivo in cardiac HL-1 cells. In vivo promoter analysis in transgenic mice revealed that the isolated alphaT-catenin promoter region could direct the tissue-specific expression of a LacZ reporter gene in concordance with endogenous alphaT-catenin expression.
ISSN:1362-4962