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Mol Cell Biol, February 1998, p. 1029-1041, Vol. 18, No. 2
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

POU Transcription Factors Brn-3a and Brn-3b Interact with the Estrogen Receptor and Differentially Regulate Transcriptional Activity via an Estrogen Response Element

Vishwanie Budhram-Mahadeo,1 Malcolm Parker,2 and David S. Latchman1,*

Medical Molecular Biology Unit, Department of Molecular Pathology, The Windeyer Institute of Medical Sciences, University College Medical School, London W1P 6DB,1 and Molecular Endocrinology Laboratories, Imperial Cancer Research Fund, London WC2A 3PX,2 United Kingdom

Received 12 March 1997/Returned for modification 30 April 1997/Accepted 19 November 1997

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.

* Corresponding author. Mailing address: Medical Molecular Biology Unit, Department of Molecular Pathology, The Windeyer Institute of Medical Sciences, University College Medical School, 46 Cleveland St., London W1P 6DB, United Kingdom. Phone: 44-171-380-9343. Fax: 44-171-387-3310. E-mail: d.latchman{at}ucl.ac.uk.




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