Functional interaction between Brn-3a and Src-1 co-activates Brn-3a-mediated transactivation.
The Brn-3a POU domain transcription factor is able to regulate the transcription of promoters containing a Brn-3 response element via its POU domain. In addition, the POU domain of Brn-3a has been shown to functionally interact with the estrogen receptor and regulate transcription from estrogen responsive promoters. The steroid receptor coactivator, Src-1, enhances transcription with a variety of steroid receptors. Here we describe a functional interaction between Brn-3a and Src-1. In glutathione S-transferase pull-down assays Src-1 was shown to specifically interact with Brn-3 proteins. Moreover, Src-1 co-immunoprecipitated from intact cells with Brn-3a. The transactivation potential of the Brn-3a/Src-1 complex was tested on both the Brn-3 responsive SNAP-25 promoter and the estrogen responsive vitellogenin promoter, in each of two different cell lines, the neuronal ND7 cell line, and the kidney BHK21 cell line. Src-1 consistently and strongly potentiated the activation of Brn-3a on the SNAP promoter construct in both the ND7 and BHK21 cell lines. The vitellogenin promoter construct, however, was only weakly activated by the Brn-3/Src-1 complex in the ND7 cells and there was even less effect on this promoter in the BHK21 cells. These results suggest a functional role for Src-1 in enhancing Brn-3a mediated transactivation, seemingly independent of nuclear hormone receptors, thus broadening the transcriptional repertoire of both Brn-3a and Src-1.
Dennis
Jonathan H
JH
Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
Budhram-Mahadeo
Vishwanie
V
Latchman
David S
DS
D000818:Animals; D002460:Cell Line; D002846:Chromatography, Affinity; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000235:genetics; D051548:Histone Acetyltransferases; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014819:Vitellogenins / Q000235:genetics
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494189:Pou4f1 protein, mouse; D011993:Recombinant Fusion Proteins; C494209:Snap25 protein, mouse; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D015534:Trans-Activators; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors; D014819:Vitellogenins; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D005982:Glutathione Transferase