Identification of a Promoter-specific Transcriptional Activation Domain at the 
C Terminus of the Wnt Effector Protein T-cell Factor 4

Hecht, Andreas; Stemmler, Marc P.

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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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Hecht, Andreas
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Stemmler, Marc P.
Emeritus Group: Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Hecht, A., & Stemmler, M. P. (2003). Identification of a Promoter-specific Transcriptional Activation Domain at the C Terminus of the Wnt Effector Protein T-cell Factor 4. Journal of Biological Chemistry, 278(6), 3776-3785.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-9572-C

Abstract

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 Cdx1 promoter, whereas LEF1 specifically activated the Siamois promoter. Deletion of a C-terminal domain of TCF4E prevented Cdx1 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 Cdx1 promoter.