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

Lymphoid Enhancer Factor-1 (LEF-1) is a member of a family of transcription factors that function as downstream mediators of the Wnt signal transducti on pathway. In the absence of Wnt signals, specific LEF/TCF isoforms repres s rather than activate gene targets through recruitment of the co-repressor CtBP, Characterization of the full-length human LEF-1 gene locus and its c omplete set of mRNA products shows that this family member exists as a uniq ue 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 can not engage in activities specific to this isoform such as recruitment of th e co-repressor CtBP, Expression of alternatively spliced LEF-1 isoforms are driven by a promoter that is highly active in lymphocyte cell lines, Trans cription initiates within a TATA-less core promoter region that contains co nsensus 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 prom oter is most active in a B lymphocyte cell line (Raji) in which the endogen ous LEF-1 gene is silent, suggesting that the promoter region is actively r epressed by a silencing mechanism.