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.
Pubmed ID: 9751710 RIS Download
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