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Originally published In Press as doi:10.1074/jbc.M313726200 on April 5, 2004

J. Biol. Chem., Vol. 279, Issue 25, 26074-26081, June 18, 2004
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Structure-Function Analysis of the Estrogen Receptor {alpha} Corepressor Scaffold Attachment Factor-B1

IDENTIFICATION OF A POTENT TRANSCRIPTIONAL REPRESSION DOMAIN*

Steven M. Townson, Kaiyan Kang, Adrian V. Lee, and Steffi Oesterreich{ddagger}

From the Departments of Medicine and Molecular and Cellular Biology, The Breast Center, Baylor College of Medicine and Methodist Hospital, Houston, Texas 77030

Scaffold attachment factor-B1 (SAFB1) is a nuclear matrix protein that has been proposed to couple chromatin structure, transcription, and RNA processing. We have previously shown that SAFB1 can repress estrogen receptor (ER{alpha})-mediated transactivation. Here we present a structure-function study showing that transactivation is mediated via an intrinsic and transferable C-terminal repression domain (RD). A similar C-terminal RD was found in the family member SAFB2. Removal of the RD from SAFB1 resulted in a dominant-negative SAFB1 protein that increased ligand-dependent and -independent ER{alpha} activity. SAFB1RD-mediated repression was partly blocked by histone deacetylase inhibitors; however, no histone deacetylase inhibitors were identified in a yeast two-hybrid screen using the RD as bait. Instead, SAFB1RD was found to interact with TAFII68, a member of the basal transcription machinery. We propose a model in which SAFB1 represses ER{alpha} activity via indirect association with histone deacetylation and interaction with the basal transcription machinery.


Received for publication, December 15, 2003 , and in revised form, March 17, 2004.

* This work was supported by Howard Temin Award KO1 (CA77674), Grant R01 (CA097213) from National Institutes of Health (to S. O.), and U. S. Army Grant DAMD17-01-1-0146 (to S. M. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: The Breast Center, Baylor College of Medicine, One Baylor Plaza, BCM 600, Houston, TX 77030. Tel.: 713-798-1623; Fax: 713-798-1642; E-mail: steffio{at}breastcenter.tmc.edu.


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