title: POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element.
abstract: The estrogen receptor (ER) modulates transcription by forming complexes with other proteins and then binding to the estrogen response element (ERE). We have identified a novel interaction of this receptor with the POU transcription factors Brn-3a and Brn-3b which was independent of ligand binding. By pull-down assays and the yeast two-hybrid system, the POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3-ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect. The POU domain of Brn-3b which interacts with the ER was sufficient to confer this activation potential, and the change of a single amino acid in the first helix of the POU homeodomain of Brn-3a to its equivalent in Brn-3b can change the mild repressive effect of Brn-3a to a stimulatory Brn-3b-like effect. These observations and their implications for transcriptional regulation by the ER are discussed.
authors.affiliation: Department of Molecular Pathology, The Windeyer Institute of Medical Sciences, University College Medical School, London, United Kingdom.
authors.forename: V
authors.initials: V
authors.lastname: Budhram-Mahadeo
authors.forename: M
authors.initials: M
authors.lastname: Parker
authors.forename: D S
authors.initials: DS
authors.lastname: Latchman
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D008970:Molecular Weight; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000378:metabolism*; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014633:Valine / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C494188:POU4F1 protein, human; C494190:POU4F2 protein, human; D011960:Receptors, Estrogen; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors; D007532:Isoleucine; D004247:DNA; D014633:Valine