COUP-TF acts as a competitive repressor for estrogen receptor-mediated activation of the mouse lactoferrin gene.
We previously demonstrated that the estrogen response module (mERM) of the mouse lactoferrin gene, which contains an overlapping chicken ovalbumin upstream promoter transcription factor (COUP-TF)- and estrogen receptor-binding element, is responsible for estrogen induction. In this report we show that COUP-TF represses the mERM response to estrogen stimulation. Mutation and deletion of the COUP-TF-binding element or reduction of the endogenous COUP-TF increases mERM estrogen responsiveness. Likewise, overexpression of the COUP-TF expression vector blocked the estrogen-stimulated response of mERM in transfected cells. The molecular mechanism of this repression is due to the competition between COUP-TF and the estrogen receptor for binding at identical contact sites in the overlapping region of the mERM. Our results indicate that two members of the steroid-thyroid receptor superfamily work in concert to modulate lactoferrin gene expression.
Liu
Y
Y
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Yang
N
N
Teng
C T
CT
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D051838:COUP Transcription Factor I; D002645:Chickens / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007781:Lactoferrin / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011960:Receptors, Estrogen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; C497590:Nr2f1 protein, mouse; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D007781:Lactoferrin