Positive and negative regulation of the transforming growth factor beta/activin target gene goosecoid by the TFII-I family of transcription factors.
Goosecoid (Gsc) is a homeodomain-containing transcription factor present in a wide variety of vertebrate species and known to regulate formation and patterning of embryos. Here we show that in embryonic carcinoma P19 cells, the transcription factor TFII-I forms a complex with Smad2 upon transforming growth factor beta (TGFbeta)/activin stimulation, is ... recruited to the distal element (DE) of the Gsc promoter, and activates Gsc transcription. Downregulation of endogenous TFII-I by small inhibitory RNA in P19 cells abolishes the TGFbeta-mediated induction of Gsc. Similarly, Xenopus embryos with endogenous TFII-I expression downregulated by injection of TFII-I-specific antisense oligonucleotides exhibit decreased Gsc expression. Unlike TFII-I, the related factor BEN (binding factor for early enhancer) is constitutively recruited to the distal element in the absence of TGFbeta/activin signaling and is replaced by the TFII-I/Smad2 complex upon TGFbeta/activin stimulation. Overexpression of BEN in P19 cells represses the TGFbeta-mediated transcriptional activation of Gsc. These results suggest a model in which TFII-I family proteins have opposing effects in the regulation of the Gsc gene in response to a TGFbeta/activin signal.
Mesh Terms:
Activins, Animals, Blotting, Northern, COS Cells, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA-Binding Proteins, Down-Regulation, Female, Gene Expression Regulation, Gene Expression Regulation, Developmental, Glutathione Transferase, Goosecoid Protein, Green Fluorescent Proteins, Homeodomain Proteins, Humans, Immunoblotting, Immunoprecipitation, Luciferases, Mice, Microscopy, Fluorescence, Models, Biological, Nodal Protein, Oligonucleotides, Antisense, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, RNA, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Smad2 Protein, Time Factors, Trans-Activators, Transcription Factors, Transcription Factors, TFII, Transcription, Genetic, Transcriptional Activation, Transforming Growth Factor beta, Up-Regulation, Xenopus, Xenopus Proteins, Xenopus laevis
Activins, Animals, Blotting, Northern, COS Cells, Cell Line, Tumor, Chromatin Immunoprecipitation, DNA-Binding Proteins, Down-Regulation, Female, Gene Expression Regulation, Gene Expression Regulation, Developmental, Glutathione Transferase, Goosecoid Protein, Green Fluorescent Proteins, Homeodomain Proteins, Humans, Immunoblotting, Immunoprecipitation, Luciferases, Mice, Microscopy, Fluorescence, Models, Biological, Nodal Protein, Oligonucleotides, Antisense, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, RNA, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Smad2 Protein, Time Factors, Trans-Activators, Transcription Factors, Transcription Factors, TFII, Transcription, Genetic, Transcriptional Activation, Transforming Growth Factor beta, Up-Regulation, Xenopus, Xenopus Proteins, Xenopus laevis
Mol. Cell. Biol.
Date: Aug. 01, 2005
PubMed ID: 16055724
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