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Cited by 101Wnt/β-catenin signaling in development and cancerGenomics and Chromatin DynamicsRNA Research and Splicing

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

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Hovanes, K., Li, T. W. H., Waterman, M. L.·2000·Nucleic Acids Research
DOI 10.1093/nar/28.9.1994PMC PMC103301
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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.

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Cited by

Sorted by citations

Authors
Hovanes, K., Li, T. W. H., & Waterman, M. L.
Affiliations
University of California, Irvine (US)
ORCID
Waterman, M. L.
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2000-05-01
Volume
28
Issue
9
Pages
1994-2003
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/28.9.1994
PMC
PMC103301
OpenAlex
W2139146322
Cited by
101
References
0
Citations by year
2026: 1 · 2025: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 5 · 2015: 3 · 2014: 6 · 2013: 2 · 2012: 4
FWCI
2.05
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
LEF1, lymphoid enhancer factor 1, Wnt signaling, transcription factors, alternative splicing, protein isoforms, promoter, lymphocytes, B cells, TATA-less promoter, Sp1 binding site, E-box, initiator element, gene silencing
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Cell Line, DNA, DNA-Binding Proteins, Exons, Gene Expression Regulation, Genes, HeLa Cells, Humans, Introns, Luciferases, Lymphocytes, Male, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Recombinant Fusion Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Sequence Alignment, PC12 Cells, Conserved Sequence, Sequence Deletion, Sequence Homology, Amino Acid, Alternative Splicing, Sequence Analysis, DNA, Jurkat Cells, COS Cells, Protein Isoforms, Rats, Lymphoid Enhancer-Binding Factor 1

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