Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4.
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.
Hecht
Andreas
A
Max-Planck-Institut für Immunbiologie, Stübeweg 51, D-79108 Freiburg, Germany. hecht@mm11.ukl.uni-freiburg.de
Stemmler
Marc P
MP
D000818:Animals; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D051820:TCF Transcription Factors; D015534:Trans-Activators / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D051176:beta Catenin
C491273:CDX1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C491272:Cdx1 protein, mouse; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse