Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex.
The proximal region of the ovalbumin gene promoter contains a half-palindromic estrogen-responsive element (ERE) that mediates cell-specific trans-activation by the estrogen receptor (ER). We show that the ovalbumin ERE binds a ubiquitous nucleoprotein complex containing oncoproteins c-Fos and c-Jun. Mutations altering the estrogen inducibility of the promoter prevent the complex formation, which is, however, found in the presence and absence of ER and estradiol. Mutagenesis indicates that the sequence 5'-TGGGTCA-3', containing the half-palindromic ERE, is responsible for induction by phorbol esters of the ovalbumin promoter and is a target for c-fos and c-jun trans-activation. Transfection experiments reveal that c-fos, c-jun, and ER coactivate the ovalbumin promoter. Direct ER interaction with the target sequence is not required, since an ER deleted for its DNA binding domain is functional in the coactivation with c-fos and c-jun. Our data indicate a convergence of hormonal induction and activation of signal transduction pathways at the transcriptional level.
Gaub
M P
MP
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
Bellard
M
M
Scheuer
I
I
Chambon
P
P
Sassone-Corsi
P
P
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002642:Chick Embryo; D005576:Colforsin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D015345:Oligonucleotide Probes; D010047:Ovalbumin / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D011960:Receptors, Estrogen / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011960:Receptors, Estrogen; D014157:Transcription Factors; D005576:Colforsin; D010047:Ovalbumin; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate