Published online 9 August 2004
Nucleic Acids Research, Vol. 32 No. 14 © Oxford University Press 2004; all rights reserved
GATA-4 and MEF2C transcription factors control the tissue-specific expression of the 
T-catenin gene CTNNA3
Unit of Molecular and Cellular Oncology and 1 Molecular Cell Biology Unit, Department for Molecular Biomedical Research, VIB-Ghent University, B-9052 Ghent-Zwijnaarde, Belgium
* To whom correspondence should be addressed. Tel: +32 9 3313740/3313600; Fax: +32 9 3313609; Email: geert.berx{at}dmbr.Ugent.be
Present address: Griet Vanpoucke, MRC—Human Reproductive Sciences Unit, 49, Little France Crescent, Edinburgh EH16 4SB, UK
Received April 6, 2004; Revised and Accepted July 9, 2004
T-catenin is a recently identified member of the -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 -catenins, T-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 T-catenin expression is controlled by its promoter region. By in silico analysis, we found that the T-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 T-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 T-catenin promoter activity in these cells. Furthermore, we showed that the GATA-4 transcription factor specifically binds and activates the T-catenin promoter in vivo in cardiac HL-1 cells. In vivo promoter analysis in transgenic mice revealed that the isolated T-catenin promoter region could direct the tissue-specific expression of a LacZ reporter gene in concordance with endogenous T-catenin expression.
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