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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.

Hecht A, Stemmler MP
The Journal of biological chemistry


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 beta-catenin and one of the four members of the T-cell factor (TCF) family of DNA-binding proteins. How can the Wnt/beta-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 beta-catenin/TCF-regulated promoters. We found that TCF4E but not LEF1 supported beta-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 beta-catenin and p300 to form a specialized transcription factor complex that specifically supports the activation of the Cdx1 promoter.

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