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.
Ku
Manching
M
Molecular Cardiology Research Institute, Tufts-New England Medical Center, Boston, MA 02111, USA.
Sokol
Sergei Y
SY
Wu
Jack
J
Tussie-Luna
Maria Isabel
MI
Roy
Ananda L
AL
Hata
Akiko
A
D028341:Activins / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D005982:Glutathione Transferase / Q000378:metabolism; D051956:Goosecoid Protein; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D055457:Nodal Protein; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051899:Smad2 Protein; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D019473:Transcription Factors, TFII / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation; D014981:Xenopus; D029867:Xenopus Proteins; D014982:Xenopus laevis
D004268:DNA-Binding Proteins; C497992:GSC protein, human; C104259:GTF2I protein, human; D051956:Goosecoid Protein; C497993:Gsc protein, mouse; D018398:Homeodomain Proteins; C526007:NODAL protein, human; D055457:Nodal Protein; C526008:Nodal protein, mouse; D016376:Oligonucleotides, Antisense; D012097:Repressor Proteins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C497785:Smad2 protein, Xenopus; C497783:Smad2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D019473:Transcription Factors, TFII; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; D028341:Activins; D049452:Green Fluorescent Proteins; D012313:RNA; D008156:Luciferases; D005982:Glutathione Transferase