Published in: Molecular and Cellular Biology,
vol. 20, no. 6, pp. 2004-2013 (March, 2000):
"Recruitment of the SWI-SNF Chromatin
Remodeling Complex as a Mechanism of Gene Activation by the Glucocorticoid
Receptor tau1 Activation Domain".
Annika E. Wallberg 1*, Kristen E. Neely 2, Ahmed H. Hassan 2, Jan-Ake Gustafsson 1, Jerry L. Workman 2, and Anthony P. H. Wright 3.
1 Karolinska Institute, Department of Biosciences, NOVUM,
S-14157 Huddinge, Sweden, and
3 Sodertorns hogskola, S-14104 Huddinge, Sweden.
2 Howard Hughes Medical Institute, Department of Biochemistry
and Molecular Biology, The Pennsylvania State University, University Park,
Pennsylvania 16802-4500.
* Corresponding author. Mailing address: The Rockefeller
University, Box 166, c/o Roeder Lab, 1230 York Ave., New York, NY 10021,
Phone: (212) 327-7604, Fax: (212) 327-7949,
E-mail: wallbea@rockvax.rockefeller.edu
Abstract:
The SWI-SNF complex has been shown to alter nucleosome conformation in an ATP-dependent manner, leading to increased accessibility of nucleosomal DNA to transcription factors. In this study, we show that the SWI-SNF complex can potentiate the activity of the glucocorticoid receptor (GR) through the N-terminal transactivation domain, tau1, in both yeast and mammalian cells. GR-tau1 can directly interact with purified SWI-SNF complex, and mutations in tau1 that affect the transactivation activity in vivo also directly affect tau1 interaction with SWI-SNF. Furthermore, the SWI-SNF complex can stimulate tau1-driven transcription from chromatin templates in vitro. Taken together, these results support a model in which the GR can directly recruit the SWI-SNF complex to target promoters during glucocorticoid-dependent gene activation. We also provide evidence that the SWI-SNF and SAGA complexes represent independent pathways of tau1-mediated activation but play overlapping roles that are able to compensate for one another under some conditions.
1. Herstein PR, and Frenster JH, "Mated Models of Gene Regulation in Eukaryotes".
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