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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activins / metabolism
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Animals
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Blotting, Northern
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COS Cells
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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DNA-Binding Proteins / metabolism
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Down-Regulation
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Female
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Gene Expression Regulation*
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Gene Expression Regulation, Developmental
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Glutathione Transferase / metabolism
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Goosecoid Protein
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Green Fluorescent Proteins / metabolism
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Homeodomain Proteins / metabolism*
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Humans
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Immunoblotting
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Immunoprecipitation
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Luciferases / metabolism
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Mice
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Microscopy, Fluorescence
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Models, Biological
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Nodal Protein
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Oligonucleotides, Antisense / pharmacology
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Plasmids / metabolism
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Promoter Regions, Genetic
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Protein Binding
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Protein Biosynthesis
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Protein Structure, Tertiary
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RNA / metabolism
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Repressor Proteins / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Smad2 Protein
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Time Factors
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Trans-Activators / metabolism
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Transcription Factors / metabolism*
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Transcription Factors, TFII / metabolism*
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Transcription, Genetic
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Transcriptional Activation
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Transforming Growth Factor beta / metabolism*
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Up-Regulation
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Xenopus
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Xenopus Proteins
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Xenopus laevis
Substances
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DNA-Binding Proteins
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GSC protein, human
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GTF2I protein, human
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Goosecoid Protein
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Gsc protein, mouse
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Homeodomain Proteins
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NODAL protein, human
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Nodal Protein
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Nodal protein, mouse
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Oligonucleotides, Antisense
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Repressor Proteins
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SMAD2 protein, human
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Smad2 Protein
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Smad2 protein, Xenopus
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Smad2 protein, mouse
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Trans-Activators
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Transcription Factors
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Transcription Factors, TFII
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Transforming Growth Factor beta
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Xenopus Proteins
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Activins
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Green Fluorescent Proteins
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RNA
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Luciferases
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Glutathione Transferase