Journal of Biological Chemistry
Volume 278, Issue 6, 7 February 2003, Pages 3776-3785
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MECHANISMS OF SIGNAL TRANSDUCTION
Identification of a Promoter-specific Transcriptional Activation Domain at the C Terminus of the Wnt Effector Protein T-cell Factor 4*

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Wnt growth factors control numerous cell fate decisions in development by altering specific gene expression patterns through the activity of heterodimeric transcriptional activators. These consist of β-catenin and one of the four members of the T-cell factor (TCF) family of DNA-binding proteins. How can the Wnt/β-catenin pathway control various sets of target genes in distinct cellular settings with such a limited number of nuclear effectors? Here we asked whether different TCF proteins could perform specific, nonredundant functions at natural β-catenin/TCF-regulated promoters. We found that TCF4E but not LEF1 supported β-catenin-dependent activation of the Cdx1promoter, whereas LEF1 specifically activated the Siamoispromoter. Deletion of a C-terminal domain of TCF4E preventedCdx1 promoter induction. A chimeric protein consisting of LEF1 and the C terminus of TCF4E was fully functional. Therefore, the TCF4E C terminus harbors a promoter-specific transactivation domain. This domain influences the DNA binding properties of TCF4 and additionally mediates an interaction with the transcriptional coactivator p300. Apparently, the C terminus of TCF4E cooperates with β-catenin and p300 to form a specialized transcription factor complex that specifically supports the activation of the Cdx1promoter.

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Published, JBC Papers in Press, November 22, 2002, DOI 10.1074/jbc.M210081200

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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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This work was done in partial fulfillment of Ph.D. requirements at the University of Freiburg.