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This version published online on October 17, 2002
Molecular Endocrinology, doi:10.1210/me.2002-0280
Molecular Endocrinology Vol. 0, No. 2002 200202801-
doi:10.1210/me.2002-0280
Copyright © 2002 by the Endocrine Society.
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Submitted on August 13, 2002
Accepted on October 7, 2002

A Novel Estrogen Receptor Alpha Associated Protein, Template Activating Factor I Beta, Inhibits Acetylation and Transactivation

Margaret A. Loven1, Nemone Muster1, John R. Yates1, and Ann M. Nardulli1*

1 Department of Molecular and Integrative Physiology, University of Illinois, Urbana, Illinois 61801; Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; University of Illinois, Urbana, Illinois 61801

* To whom correspondence should be addressed. E-mail: anardull{at}life.uiuc.edu.

Estrogen receptor {alpha} (ER{alpha}) functions as a ligand-activated transcription factor that alters expression of estrogen-responsive genes in target cells. Numerous regulatory proteins interact with ER{alpha} to influence estrogen-mediated transactivation. We have identified a novel coregulatory protein, template activating factor-Iß (TAF-Iß), which binds to ER{alpha} in vitro when the receptor is not complexed with an estrogen response element. The central region of TAF-Iß interacts with both the DNA binding domain and the carboxy terminal region of ER{alpha}. Coimmunoprecipitation experiments demonstrate that TAF-Iß is associated with the unoccupied, but not the estrogen-occupied ER{alpha} in MCF-7 breast cancer cells. Overexpression of TAF-Iß inhibits ER{alpha}-mediated transcription in a dose-dependent manner. TAF-Iß represses p300-mediated acetylation of histones and ER{alpha} in vitro and decreases ER{alpha} acetylation in vivo. TAF-Iß also binds to other nuclear receptor superfamily members and represses thyroid hormone receptor ß-induced transcription in transient transfection assays. Taken together, these data provide evidence that TAF-Iß regulates transcription of estrogen-responsive genes by modulating acetylation of histones and ER{alpha} and that TAF-Iß's effects extend to other nuclear receptor superfamily members as well.
Key words: estrogen receptor • template activating factor I • transcription

NURSA Molecule Pages Link:

Nuclear Receptors:   TRβ  |  RXRα  |  ERα  |  PR
Coregulators:   p300
Ligands:   17β-Estradiol  |  9-cis-Retinoic acid  |  Progesterone  |  Thyroid hormone



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