Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors.
The mammalian AML/CBFalpha runt domain (RD) transcription factors regulate hematopoiesis and osteoblast differentiation. Like their Drosophila counterparts, most mammalian RD proteins terminate in a common pentapeptide, VWRPY, which serves to recruit the corepressor Groucho (Gro). Using a yeast two-hybrid assay, in vitro association and pull-down experiments, we demonstrate that Gro ... and its mammalian homolog TLE1 specifically interact with AML1 and AML2. In addition to the VWRPY motif, other C-terminal sequences are required for these interactions with Gro/TLE1. TLE1 inhibits AML1-dependent transactivation of the T cell receptor (TCR) enhancers alpha and beta, which contain functional AML binding sites, in transfected Jurkat T cells. LEF-1 is an additional transcription factor that mediates transactivation of TCR enhancers. LEF-1 and its Drosophila homolog Pangolin (Pan) are involved in the Wnt/Wg signaling pathway through interactions with the coactivator beta-catenin and its highly conserved fly homolog Armadillo (Arm). We show that TLE/Gro interacts with LEF-1 and Pan, and inhibits LEF-1:beta-catenin-dependent transcription. These data indicate that, in addition to their activity as transcriptional activators, AML1 and LEF-1 can act, through recruitment of the corepressor TLE1, as transcriptional repressors in TCR regulation and Wnt/Wg signaling.
Mesh Terms:
Amino Acid Sequence, Animals, Armadillo Domain Proteins, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Cell Line, Core Binding Factor Alpha 2 Subunit, Cytoskeletal Proteins, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Genes, Reporter, Humans, Insect Proteins, Lymphoid Enhancer-Binding Factor 1, Neoplasm Proteins, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Receptors, Antigen, T-Cell, alpha-beta, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae, Trans-Activators, Transcription Factors, Transfection, beta Catenin
Amino Acid Sequence, Animals, Armadillo Domain Proteins, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Cell Line, Core Binding Factor Alpha 2 Subunit, Cytoskeletal Proteins, DNA-Binding Proteins, Drosophila, Drosophila Proteins, Genes, Reporter, Humans, Insect Proteins, Lymphoid Enhancer-Binding Factor 1, Neoplasm Proteins, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Receptors, Antigen, T-Cell, alpha-beta, Recombinant Fusion Proteins, Repressor Proteins, Saccharomyces cerevisiae, Trans-Activators, Transcription Factors, Transfection, beta Catenin
Proc. Natl. Acad. Sci. U.S.A.
Date: Sep. 29, 1998
PubMed ID: 9751710
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