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Molecular and Cellular Biology, April 2006, p. 3204-3214, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3204-3214.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Thyroid Hormone Receptor {alpha}1 Directly Controls Transcription of the ß-Catenin Gene in Intestinal Epithelial Cells{dagger}

Michelina Plateroti,1* Elsa Kress,1 Jun Ichirou Mori,1 and Jacques Samarut1,2

IFR 128, Laboratoire de Biologie Moléculaire de la Cellule, Biosciences,CNRS UMR 5161, INRA UMR 1237, Ecole Normale Supérieure de Lyon, Lyon, France,1 Université Claude Bernard Lyon 1, Lyon, France2

Received 29 July 2005/ Returned for modification 30 September 2005/ Accepted 17 January 2006

Thyroid hormones, T3 and T4, are known regulators of intestine development. The best characterized example is the remodeling of the gastrointestinal tract during amphibian metamorphosis. Thyroid hormones act via nuclear receptors, the TRs, which are T3-dependent transcription factors. We previously showed that intestinal epithelial cell proliferation is controlled by thyroid hormones and the TR{alpha} gene. To analyze the mechanisms responsible, we studied the expression of genes belonging to and/or activated by the Wnt/ß-catenin pathway, a major actor in the control of physiological and pathological epithelial proliferation in the intestine. We show that T3-TR{alpha}1 controls the transcription of the ß-catenin gene in an epithelial cell-autonomous way. This is parallel to positive regulation of proliferation-controlling genes such as type D cyclins and c-myc, known targets of the Wnt/ß-catenin. In addition, we show that the regulation of the ß-catenin gene is direct, as TR binds in vitro and in chromatin in vivo to a specific thyroid hormone-responsive element present in intron 1 of this gene. This is the first report concerning in vivo transcriptional control of the ß-catenin gene. As Wnt/ß-catenin plays a crucial role in intestinal tumorigenesis, our observations open a new perspective on the study of TRs as potential tumor inducers.

* Corresponding author. Mailing address: IFR 128, Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR 5161, INRA UMR 1237, Ecole Normale Supérieure de Lyon, 46, Allee d'Italie, Lyon 69364, France. Phone: 33 4 72728616. Fax: 33 4 72 72 80 80. E-mail: Michela.Plateroti{at}ens-lyon.fr.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org.

Molecular and Cellular Biology, April 2006, p. 3204-3214, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3204-3214.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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