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J. Biol. Chem., Vol. 277, Issue 31, 28247-28255, August 2, 2002
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From the The glucocorticoid receptor (GR) contains several
activation domains,
Glucocorticoid Receptor Domain Requirements for Chromatin
Remodeling and Transcriptional Activation of the Mouse Mammary Tumor
Virus Promoter in Different Nucleoprotein Contexts*
§,
Department of Genetics, George Washington
University, Washington, D. C. and the § Laboratory of
Receptor Biology and Gene Expression, Center for Cancer Research, NCI,
National Institutes of Health, Bethesda, Maryland 20852
1 (AF-1), 2, and AF-2, which were initially
defined using transiently transfected reporter constructs. Using domain mutations in the context of full-length GR, this study defines those
domains required for activation of the mouse mammary tumor virus (MMTV)
promoter in two distinct nucleoprotein configurations. A transiently
transfected MMTV template with a disorganized, accessible chromatin
structure was largely dependent on the AF-2 domain for activation. In
contrast, activation of an MMTV template in organized, replicated
chromatin requires both domains but has a relatively larger dependence
on the 1 domain. Domain requirements for GR-induced chromatin
remodeling of the latter template were also investigated. Mutation of
the AF-2 helix 12 domain partially inhibits the induction of nuclease
hypersensitivity, but the inhibition was relieved in the absence of
1, suggesting the occurrence of an important interaction between the
two domains. Further mutational analysis indicates that GR-induced
chromatin remodeling requires the ligand-binding domain in the region
of helix 3. Our study shows that the GR activation surfaces required
for transcriptional modulation of a target promoter were determined in
part by its chromatin structure. Within a particular cellular
environment the GR appears to possess a significant degree of
versatility in the mechanism by which it activates a target promoter.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: National
Institutes of Health, Laboratory of Receptor Biology and Gene
Expression, Bldg. 41, Rm. B608, 41 Library Dr. MSC 5055, Bethesda, MD
20892-5055. Tel.: 301-496-7538; Fax: 301-496-4951; E-mail:
smithcat@exchange.nih.gov.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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