Journal of Biological Chemistry
Volume 277, Issue 16, 19 April 2002, Pages 14159-14171
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MOLECULAR BASIS OF CELL AND DEVELOPMENTAL BIOLOGY
Functional Diversity of Xenopus Lymphoid Enhancer Factor/T-cell Factor Transcription Factors Relies on Combinations of Activating and Repressing Elements*

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Lymphoid enhancer factor/T-cell factor (LEF/TCF) high mobility group box transcription factors are the nuclear transducers of the Wnt/β-catenin signaling cascade. InXenopus, three members of the LEF/TCF family, XLEF-1, XTCF-3, and XTCF-4, with distinct but partially overlapping expression patterns have been identified. The individual XenopusLEF/TCF family members differ extremely in their properties of target gene regulation. We observed that in contrast to LEF-1, neither XTCF-3 nor XTCF-4 can induce secondary axis formation upon ventral overexpression in Xenopus embryos. To identify functional motifs within the LEF/TCF transcription factors responsible for target gene activation or repression, we created various mutants and a set of XLEF-1/XTCF-3 chimeras. In overexpression studies, we asked whether these constructs can mimic an activated Wnt/β-catenin pathway and lead to the formation of a secondary body axis. In addition, we examined their capacity to rescue a loss-of-function phenotype given by dominant negative LEF-1 expression. We further analyzed their ability to directly activate target genes in reporter gene assays using the LEF/TCF target promoters, siamois and fibronectin. We found that a region homologous to exon IVa of human TCF-1 is an activating element. This is flanked by two small repressing motifs, LVPQ and SXXSS. Our findings implicate that the motifs identified here play an essential role in determining cell type-specific activity of LEF/TCF transcription factors.

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Published, JBC Papers in Press, January 30, 2002, DOI 10.1074/jbc.M107055200

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This work was supported by the Deutsche Forschungsgemeinschaft and the Verband der Chemischen Industrie.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.