Positive and negative regulation of the transforming growth factor beta/activin target gene goosecoid by the TFII-I family of transcription factors.

Abstract	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.
Authors	Manching Ku, Sergei Y Sokol, Jack Wu, Maria Isabel Tussie-Luna, Ananda L Roy, Akiko Hata
Journal	Molecular and cellular biology (Mol Cell Biol) Vol. 25 Issue 16 Pg. 7144-57 (Aug 2005) ISSN: 0270-7306 [Print] United States
PMID	16055724 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	DNA-Binding Proteins GSC protein, human GTF2I protein, human Goosecoid Protein Gsc protein, mouse Homeodomain Proteins NODAL protein, human Nodal Protein Nodal protein, mouse Oligonucleotides, Antisense Repressor Proteins SMAD2 protein, human Smad2 Protein Smad2 protein, Xenopus Smad2 protein, mouse Trans-Activators Transcription Factors Transcription Factors, TFII Transforming Growth Factor beta Xenopus Proteins Activins Green Fluorescent Proteins RNA Luciferases Glutathione Transferase
Topics	Activins (metabolism) Animals Blotting, Northern COS Cells Cell Line, Tumor Chromatin Immunoprecipitation DNA-Binding Proteins (metabolism) Down-Regulation Female Gene Expression Regulation Gene Expression Regulation, Developmental Glutathione Transferase (metabolism) Goosecoid Protein Green Fluorescent Proteins (metabolism) Homeodomain Proteins (metabolism) Humans Immunoblotting Immunoprecipitation Luciferases (metabolism) Mice Microscopy, Fluorescence Models, Biological Nodal Protein Oligonucleotides, Antisense (pharmacology) Plasmids (metabolism) Promoter Regions, Genetic Protein Binding Protein Biosynthesis Protein Structure, Tertiary RNA (metabolism) Repressor Proteins (metabolism) Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Smad2 Protein Time Factors Trans-Activators (metabolism) Transcription Factors (metabolism) Transcription Factors, TFII (metabolism) Transcription, Genetic Transcriptional Activation Transforming Growth Factor beta (metabolism) Up-Regulation Xenopus Xenopus Proteins Xenopus laevis

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