POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element.

Molecular and Cellular Biology
Vishwanie S Budhram-MahadeoD S Latchman

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.

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Citations

Jan 31, 2006·Expert Opinion on Therapeutic Targets·Vishwanie S Budhram-Mahadeo, David S Latchman
Sep 10, 2005·International Journal of Cancer. Journal International Du Cancer·Laila SamadyDavid S Latchman
Jun 8, 2002·Biochemical and Biophysical Research Communications·Jonathan H DennisDavid S Latchman
May 7, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Adam J KuhlMarius Brouwer
Nov 9, 2005·Prostate Cancer and Prostatic Diseases·J K J DissD S Latchman
Nov 2, 2004·Nature Reviews. Immunology·Laurie H GlimcherGraham M Lord
Mar 17, 2010·The Journal of Biological Chemistry·Daniel C BerwickDavid S Latchman
Sep 8, 2000·Molecular Endocrinology·M RazandiE R Levin
Oct 24, 2000·Molecular Endocrinology·F GayG Salbert
Sep 16, 2000·The Journal of Biological Chemistry·M RazandiE R Levin
Jun 26, 1999·The Journal of Biological Chemistry·T KakizawaK Hashizume
May 18, 1999·The Journal of Biological Chemistry·V Budhram-MahadeoD S Latchman
Jan 28, 1999·The Journal of Biological Chemistry·A M MoilanenJ J Palvimo
Sep 22, 1999·Molecular and Cellular Biology·B A AmendtA F Russo
Feb 19, 2004·The Journal of Biological Chemistry·Shazia IrshadVishwanie Budhram-Mahadeo
Jan 7, 2000·Biochemical and Biophysical Research Communications·T NakanoS Aizawa
May 3, 2021·Computational Biology and Chemistry·Jeremias IvanDavid Agustriawan

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