title: The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, CA 92697-4025, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hovanes
authors.forename: T W
authors.initials: TW
authors.lastname: Li
authors.forename: M L
authors.initials: ML
authors.lastname: Waterman
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D019556:COS Cells; D002460:Cell Line; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D019169:Jurkat Cells; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1; D008297:Male; D008969:Molecular Sequence Data; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C497573:LEF1 protein, human; C497575:Lef1 protein, rat; D051821:Lymphoid Enhancer-Binding Factor 1; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases