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Molecular Endocrinology, doi:10.1210/me.2002-0280
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Molecular Endocrinology 17 (1): 67-78
Copyright © 2003 by The Endocrine Society

A Novel Estrogen Receptor {alpha}-Associated Protein, Template-Activating Factor Iß, Inhibits Acetylation and Transactivation

Margaret A. Loven, Nemone Muster, John R. Yates and Ann M. Nardulli

Department of Molecular and Integrative Physiology (M.L., A.M.N.), University of Illinois, Urbana, Illinois 61801; and Department of Cell Biology (N.M., J.R.Y.), The Scripps Research Institute, La Jolla, California 92037

Address all correspondence and requests for reprints to: Ann M. Nardulli, Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, 524 Burrill Hall, 407 South Goodwin Avenue, Urbana, Illinois 61801. 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 the effects of TAF-Iß extend to other nuclear receptor superfamily members as well.

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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