Chromatin remodeling complexes involved in gene activation by the glucocorticoid receptor
Author: Wallberg, Annika
Date: 1999-12-17
Location: Hörsalen, plan 4, Novum
Time: 10.00
Department: Biovetenskaper och näringslära / Biosciences and Nutrition
Abstract
The glucocorticoid receptor (GR) belongs to a large family of
ligand-inducible nuclear receptors and consists of a ligand binding
domain, a DNA binding domain and transactivation domains. The main
transcriptional activation domain, c I, is located in the N-terminus of
the receptor. The r I c represents the minimal core activation domain of
rl. We have studied the molecular mechanisms by which the GR can activate
transcription through its N-terminal transactivation domain [tau]1 domain
or [tau]1c.
We have shown that the vIc, can interact with purified proteins domain
domain and CBP. In addition, the rl can interact with purified histone
acetyltransferase (HAT) complexes SAGA and domain and the domain
chromatin remodeling complex. Interestingly, mutations in rl that affect
the transactivation activity in vivo, also directly affect rl-interaction
with all of the target factors we have tested (i.e. domain TBP, CBP,
SAGA, SWl/SNF), indicating that these factors share binding determinants
on [tau]1.
The activity of the cl mutants in vivo also correlates with their
activity in an in vitro transcription assay with target factors present.
Both SAGA and domain can stimulate GAL4-[tau]1-driven transcription from
chromatin templates in vitro and the transcriptional efficiency is
affected by mutations in the rl domain. The SWI/SNF complex can also
potentiate rl-driven transcription from chromatin templates in vitro.
These results indicate that [tau]1 may mediate transactivation in vivo
through the recruitment of multiple chromatin remodeling complexes to the
promoters of target genes.
By measuring the activity of several r I domain with different activities
in yeast cells deficient for Ada proteins, we have shown that other gene
activation mechanisms, in addition to the Ada pathway, are involved in
the activity of the [tau]1c domain. Using the same approach, we could
determine that a SWI/SNF-independent pathway also exists in yeast,
suggesting that Ada-containing HAT complexes and the SWI/SNF complex
represent independent pathways when mediating r1c activity.
List of papers:
I. Henriksson A, Almlof T, Ford J, McEwan IJ, Gustafsson JA, Wright AP (1997). "Role of the Ada adaptor complex in gene activation by the glucocorticoid receptor. " Mol Cell Biol 17(6): 3 065-3073
Pubmed
II. Almlof T, Wallberg AE, Gustafsson JA, Wright AP (1998). "Role of important hydrophobic amino acids in the interaction between the glucocorticoid receptor tau 1-core activation domain and target factors. " Biochemistry 37(26): 9586-9594
Pubmed
III. Wallberg AE, Neely KE, Gustafsson JA, Workman JL, Wright AP, Grant PA (1999). "Histone acetyltransferase complexes can mediate transcriptional activation by the major glucocorticoid receptor activation domain." Mol Cell Biol 19(9): 5952-5959
Pubmed
IV. Wallberg AE, Neely KE, Hassan AH, Gustafsson JA, Workman JL, Wright AP (2000). "Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor tau1 activation domain. " Mol Cell Biol 20(6): 2004-2013
Pubmed
V. (2000). " "
I. Henriksson A, Almlof T, Ford J, McEwan IJ, Gustafsson JA, Wright AP (1997). "Role of the Ada adaptor complex in gene activation by the glucocorticoid receptor. " Mol Cell Biol 17(6): 3 065-3073
Pubmed
II. Almlof T, Wallberg AE, Gustafsson JA, Wright AP (1998). "Role of important hydrophobic amino acids in the interaction between the glucocorticoid receptor tau 1-core activation domain and target factors. " Biochemistry 37(26): 9586-9594
Pubmed
III. Wallberg AE, Neely KE, Gustafsson JA, Workman JL, Wright AP, Grant PA (1999). "Histone acetyltransferase complexes can mediate transcriptional activation by the major glucocorticoid receptor activation domain." Mol Cell Biol 19(9): 5952-5959
Pubmed
IV. Wallberg AE, Neely KE, Hassan AH, Gustafsson JA, Workman JL, Wright AP (2000). "Recruitment of the SWI-SNF chromatin remodeling complex as a mechanism of gene activation by the glucocorticoid receptor tau1 activation domain. " Mol Cell Biol 20(6): 2004-2013
Pubmed
V. (2000). " "
Issue date: 1999-11-26
Publication year: 1999
ISBN: 91-628-3956-X
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