Abstract
The role of Groucho/transducin-like Enhancer of split (Gro/TLE) family members as corepressors of transcription is well documented. TLX1 is a homeodomain transcription factor involved in splenogenesis and neuron formation, and its aberrant expression gives rise to T-cell acute lymphoblastic leukemia. We demonstrate by glutathione-S-transferase pull-down assays, in vivo biotinylation tagging and confocal laser microscopy that TLX1 interacts with TLE1 via an Eh1-like motif. Paradoxically, we found that this motif is essential for optimal transcriptional activation of two TLX1 target genes, Aldh1a1 and Fhl1. Using a well characterized target of the Hairy/Enhancer of split 1 (HES1).TLE1 repressor complex, the ASCL1 gene, we show that TLX1 counteraction of ASCL1 repression by HES1 in SK-N-BE(2) neuroblastoma cells is associated with dismissal of TLE1 from the ASCL1 promoter and requires the Eh1-like motif for maximal effect. Collectively, these results indicate that TLX1-mediated target gene activation can occur in part via derepression strategies involving Gro/TLE corepressors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehyde Dehydrogenase / genetics
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Aldehyde Dehydrogenase 1 Family
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Amino Acid Motifs
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Cell Line
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Cell Line, Tumor
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Co-Repressor Proteins
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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LIM Domain Proteins
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Mice
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Muscle Proteins / genetics
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Promoter Regions, Genetic
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Protein Interaction Mapping
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Retinal Dehydrogenase
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Transcriptional Activation*
Substances
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ASCL1 protein, human
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Basic Helix-Loop-Helix Transcription Factors
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Co-Repressor Proteins
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FHL1 protein, human
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Homeodomain Proteins
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Intracellular Signaling Peptides and Proteins
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LIM Domain Proteins
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Muscle Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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TLE1 protein, human
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TLX1 protein, human
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Aldehyde Dehydrogenase 1 Family
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Aldehyde Dehydrogenase
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ALDH1A1 protein, human
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Retinal Dehydrogenase