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.
Medical Molecular Biology Unit,
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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