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Molecular and Cellular Biology, September 1999, p. 5952-5959, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Histone Acetyltransferase Complexes Can Mediate
Transcriptional Activation by the Major Glucocorticoid Receptor
Activation Domain
Annika E.
Wallberg,1,*
Kristen E.
Neely,2
Jan-Åke
Gustafsson,1
Jerry L.
Workman,2
Anthony P. H.
Wright,1,3 and
Patrick A.
Grant2
Karolinska Institute, Department of
Biosciences, NOVUM, S-14157 Huddinge,1 and
Södertörns Högskola, S-14104
Huddinge,3 Sweden, and Howard Hughes
Medical Institute, Department of Biochemistry and Molecular
Biology, The Pennsylvania State University, University Park,
Pennsylvania 16802-45002
Received 18 February 1999/Returned for modification 15 April
1999/Accepted 18 June 1999
Previous studies have shown that the Ada adapter proteins are
important for glucocorticoid receptor (GR)-mediated gene activation in
yeast. The N-terminal transactivation domain of GR,
1, is dependent
upon Ada2, Ada3, and Gcn5 for transactivation in vitro and in vivo.
Using in vitro techniques, we demonstrate that the GR-
1 interacts
directly with the native Ada containing histone acetyltransferase (HAT)
complex SAGA but not the related Ada complex. Mutations in
1 that
reduce
1 transactivation activity in vivo lead to a reduced binding
of
1 to the SAGA complex and conversely, mutations increasing the
transactivation activity of
1 lead to an increased binding of
1
to SAGA. In addition, the Ada-independent NuA4 HAT complex also
interacts with
1. GAL4-
1-driven transcription from chromatin
templates is stimulated by SAGA and NuA4 in an acetyl coenzyme
A-dependent manner. Low-activity
1 mutants reduce SAGA- and
NuA4-stimulated transcription while high-activity
1 mutants increase
transcriptional activation, specifically from chromatin templates. Our
results demonstrate that the targeting of native HAT complexes by the
GR-
1 activation domain mediates transcriptional stimulation from
chromatin templates.
*
Corresponding author. Mailing address: Karolinska
Institute, Department of Biosciences, NOVUM, S-14157 Huddinge, Sweden.
Phone: 46-8-6089155. Fax: 46-8-7745538. E-mail:
annika.wallberg{at}csb.ki.se.
Molecular and Cellular Biology, September 1999, p. 5952-5959, Vol. 19, No. 9
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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