title: COUP-TF acts as a competitive repressor for estrogen receptor-mediated activation of the mouse lactoferrin gene.
abstract: 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.
authors.affiliation: Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.forename: C T
authors.initials: CT
authors.lastname: Teng
mesh_terms: 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
chemical_list: 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