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Nucleic Acids Research, 2000, Vol. 28, No. 9 1994-2003
© 2000 Oxford University Press

The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing

K. Hovanes, T. W. H. Li and M. L. Waterman*

Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, Irvine, CA 92697-4025, USA

Received November 17, 1999; Revised and Accepted February 29, 2000.

Lymphoid Enhancer Factor-1 (LEF-1) is a member of a family of transcription factors that function as downstream mediators of the Wnt signal transduction pathway. In the absence of Wnt signals, specific LEF/TCF isoforms repress rather than activate gene targets through recruitment of the co-repressor CtBP. Characterization of the full-length human LEF-1 gene locus and its complete set of mRNA products shows that this family member exists as a unique set of alternatively spliced isoforms; none are homologous to TCF-1E/TCF-4E. Therefore LEF-1 is distinct from its TCF family members in that it cannot engage in activities specific to this isoform such as recruitment of the co-repressor CtBP. Expression of alternatively spliced LEF-1 isoforms are driven by a promoter that is highly active in lymphocyte cell lines. Transcription initiates within a TATA-less core promoter region that contains consensus binding sites for Sp1, an E box, an Initiator element and a LEF/TCF binding site, all juxtaposed to the start sites of transcription. The promoter is most active in a B lymphocyte cell line (Raji) in which the endogenous LEF-1 gene is silent, suggesting that the promoter region is actively repressed by a silencing mechanism.

* To whom correspondence should be addressed. Tel: +1 949 824 2885; Fax: +1 949 824 8598; Email: mlwaterm@uci.edu


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