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Molecular and Cellular Biology, April 2004, p. 2757-2766, Vol. 24, No. 7
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.7.2757-2766.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Meox Homeodomain Proteins Are Required for Bapx1 Expression in the Sclerotome and Activate Its Transcription by Direct Binding to Its Promoter

Isabel Rodrigo,^1,2* Paola Bovolenta,¹ Baljinder S. Mankoo,³ and Kenji Imai²

Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain,¹ Institute of Developmental Genetics, GSF-National Research Center for Environment and Health, 85764 Neuherberg, Germany,² Randall Centre for Molecular Mechanisms of Cell Function, GKT School of Biomedical Sciences, King's College London, SE1 1UL London, United Kingdom³

Received 10 September 2003/ Returned for modification 25 November 2003/ Accepted 12 December 2003

The axial skeleton of vertebrates derives from the sclerotomal compartment of the somites. Genetic analysis has demonstrated that the transcription factors Pax1, Pax9, Meox1, Meox2, and Bapx1 are all required for sclerotomal differentiation. Their hierarchical relationship is, however, poorly understood. Because Bapx1 expression in the somites starts slightly later than that of the Meox genes, we asked whether Bapx1 is one of their downstream targets. Our analysis of Meox1; Meox2 mutant mice supports this hypothesis, as Bapx1 expression in the sclerotome is lost in the absence of both Meox proteins. Using transient-transfection assays, we show that Meox1 activates the Bapx1 promoter in a dose-dependent manner and that this activity is enhanced in the presence of Pax1 and/or Pax9. Furthermore, by electrophoretic mobility shift and chromatin immunoprecipitation experiments, we demonstrate that Meox1 can bind the Bapx1 promoter. The palindromic sequence TAATTA, present in the Bapx1 promoter, binds the Meox1 protein in vitro and is necessary for Meox1-induced transactivation of the Bapx1 promoter. Our data demonstrate that the Meox genes are required for Bapx1 expression in the sclerotome and suggest that the mechanism by which the Meox proteins exert this function is through direct activation of the Bapx1 gene.

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* Corresponding author. Mailing address: Instituto Cajal, Consejo Superior de Investigaciones Científicas, Dr. Arce 37, 28002 Madrid, Spain. Phone: 34-91-585 47 15. Fax: 34-91-585 47 54. E-mail: irodrigo{at}cajal.csic.es.

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Molecular and Cellular Biology, April 2004, p. 2757-2766, Vol. 24, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.7.2757-2766.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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