Glucocorticoid receptor-mediated chromatin remodeling in vivo

Deroo, Bonnie J.; Archer, Trevor

doi:10.1038/sj.onc.1204328

Cited by 81 publications

(64 citation statements)

References 60 publications

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“…UL3 cells contain a stably integrated MMTV promoter regulating a luciferase reporter. This promoter has a normal chromatin structure including distinct nucleosomes and enhanced transcription factor binding associated with chromatin remodeling (31,32). Alternatively, an MMTV promoter regulating a CAT reporter that is transiently transfected into cells has a poorly defined chromatin structure lacking clear nucleosomes or evidence of chromatin remodeling.…”

Section: Resultsmentioning

confidence: 99%

“…The effect of chromatin structure on H3 phosphorylation and osmotic response was investigated by comparing the transiently transfected MMTV promoter with a poorly organized chromatin architecture with the normal nucleosome structure of the integrated promoter (31)(32)(33). We found that osmotic stress represses hormone-dependent activation of the integrated MMTV.…”

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confidence: 99%

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Osmotic Stress-dependent Repression Is Mediated by Histone H3 Phosphorylation and Chromatin Structure

Burkhart

Kennett

Archer

2007

Journal of Biological Chemistry

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Histone H3 phosphorylation has been linked to various environmental stress responses and specific chromatin structure. The role of H3 phosphorylation in the osmotic stress response was investigated on the mouse mammary tumor virus (MMTV) promoter in different chromatin configurations. Hormone-dependent transcription from the MMTV promoter is repressed by osmotic stress when the promoter is integrated and has a normal chromatin structure. However, when the MMTV promoter is transiently transfected, the chromatin structure is less organized, and hormone induction is not affected by osmotic stress. On the integrated MMTV promoter, phosphorylation of histone H3 serine 10 and 28 increases in response to osmotic stress, but the transient promoter shows no change. Hormonedependent glucocorticoid receptor binding is reduced on the repressed promoter, and elevated H3 phosphorylation is temporally correlated with maximal MMTV repression Additionally, the protein kinase C inhibitor rottlerin, but not other kinase inhibitors, blocks both histone H3 phosphorylation and osmotic repression of MMTV transcription. Glucocorticoid receptor binding is inversely correlated with H3 phosphorylation, suggesting that displacement of the glucocorticoid receptor from the promoter is due to H3 phosphorylation and is the mechanism for the osmotic repression of hormone-dependent transcription.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Osmotic Stress-dependent Repression Is Mediated by Histone H3 Phosphorylation and Chromatin Structure

Burkhart

Kennett

Archer

2007

Journal of Biological Chemistry

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“…Histone H1 has clear effects on higher-order chromatin structure and phosphorylation of histone H1 is a critical component of GR-mediated MMTV activation (Bhattacharjee et al 2001, Georgel et al 2003. During GR-mediated chromatin remodeling, histone H1 is lost from the MMTV promoter (Bresnick et al 1992; reviewed in Deroo & Archer 2001, Hebbar & Archer 2003, Kinyamu & Archer 2004. Upon prolonged glucocorticoid exposure, the following prolonged exposure to hormone is accompanied by dephosphorylation of the global and promoter-associated histone H1 that is mimicked by kinase inhibitors (Lee & Archer 1998, Bhattacharjee et al 2001.…”

Section: Ubiquitin-proteasome and Nr-dependent Chromatin Remodeling: mentioning

confidence: 99%

“…Transcriptional regulation by the GR is concomitant with chromatin remodeling exemplified by restriction enzyme hypersensitivity on the MMTV promoter (reviewed in Deroo & Archer 2001, Hsiao et al 2002, Hebbar & Archer 2003. Proteasome inhibitors increase GR transactivation of the MMTV promoter in the absence of increased chromatin remodeling as measured by restriction enzyme hypersensitivity (Deroo et al 2002).…”

Section: Ubiquitin-proteasome and Nr-dependent Chromatin Remodeling: mentioning

confidence: 99%

Linking the ubiquitin–proteasome pathway to chromatin remodeling/modification by nuclear receptors

Kinyamu

Chen²,

Archer

2005

Journal of Molecular Endocrinology

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Over 25 years ago, eukaryotic cells were shown to contain a highly specific system for the selective degradation of short-lived proteins, this system is known as the ubiquitin-proteasome pathway. In this pathway, proteins are targeted for degradation by covalent modification by a small highly conserved protein named ubiquitin. Ubiquitin-mediated degradation of regulatory proteins plays an important role in numerous cell processes, including cell cycle progression, signal transduction and transcriptional regulation. Recent experiments have shown that the ubiquitin-proteasome pathway is also involved in nuclear hormone receptor (NR)-mediated transcriptional regulation. The idea that the ubiquitinproteasome pathway is involved in NR-mediated transcription is strengthened by experiments showing that ubiquitinproteasome components are recruited to NR target gene promoters. However, it is not clear how these components modulate NR-mediated chromatin remodeling and gene expression. In this review, we postulate the role of the ubiquitin-proteasome pathway on NR-mediated chromatin remodeling and gene regulation based on the current knowledge from studies implicating the pathway in chromatin structure modifications that are applicable to NR function. Since evidence from this laboratory, using the glucocorticoid receptor responsive mouse mammary tumor virus (MMTV) promoter organized as chromatin, suggest that the ubiquitin-proteasome system may be involved in the elongation phase of transcription, we particularly concentrate on chromatin modifications associated with the elongation phase.

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“…Direct GR AF1:TBP interaction raises the possibility that the GR AF1 domain somehow directly influences the primary transcription machinery. In vitro transcription studies indicated that the holo-GR acts to stabilize the preinitiation complex (31,32). One possibility is that a structured conformation of AF1, induced or stabilized by its interaction with TBP, is involved in the platform for TBP-associated factors.…”

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TATA box binding protein induces structure in the recombinant glucocorticoid receptor AF1 domain

Kumar

Volk

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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A number of transcription factor proteins contain domains that are fully or partially unstructured. The means by which such proteins acquire naturally folded conformations are not well understood. When they encounter their proper binding partner(s), several of these proteins adopt a folded conformation through an induced-fit mechanism. The glucocorticoid receptor (GR) is a ligand-activated transcription factor. Expressed independently as a recombinant peptide, the N-terminal transactivation domain (AF1) of the GR shows little structure and appears to exist as a collection of random coil configurations. The GR AF1 is known to interact with other transcription factors, including a critical component of the general transcription machinery proteins, the TATA box binding protein (TBP). We tested whether this interaction can lead to acquisition of structure in the GR AF1. Our results show that recombinant GR AF1 acquires a significant amount of helical content when it interacts with TBP. These structural changes were monitored by Fourier transform infrared and NMR spectroscopies, and by proteolytic digestions. Our results support a model in which TBP binding interaction with the GR AF1 induces significantly greater helical structure in the AF1 domain. This increased helical content in the GR AF1 appears to come mostly at the expense of random coil conformation. These results are in accordance with the hypothesis that an induced-fit mechanism gives structure to the GR AF1 when it encounters TBP.glucocorticoid receptor ͉ N-terminal activation function ͉ coregulatory protein ͉ protein folding T he glucocorticoid receptor (GR) is a ligand-activated transcription factor with the domain structural arrangement typical of the nuclear hormone receptors superfamily (1-4). The GR regulates transcription of target genes by binding DNA at specific hormone response elements and͞or by interacting with other transcription factors (5-8). Although the structural organization of steroid receptors into N-terminal domain (NTD), DNA binding domain (DBD), and ligand binding domain is well characterized (9-14), precisely how transcription is regulated by them is largely unknown. For all steroid receptors, this is in part due to the lack of information about their transcription activating domain AF1, located in the NTD (9, 10). The GR AF1 sequence resembles those of acidic transactivation domains of several transcription factors (15, 16). When expressed independently, the GR AF1 shows little structure and seems to exist as an ensemble of largely unstructured conformers (17, 18). The GR AF1 is known to interact with other transcription factors, and conditional folding has been suggested to be the key for these interactions (19)(20)(21)(22).It has been reported that in the presence of trifluoroethanol, the ''core'' of AF1 (AF1 c , amino acids 187-242), located toward the C-terminal end of AF1, adopts three helical segments (17). Independent experiments have shown that substitution of the ␣-helixbreaking amino acid proline for natural residues a...

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Glucocorticoid receptor-mediated chromatin remodeling in vivo

Cited by 81 publications

References 60 publications

Osmotic Stress-dependent Repression Is Mediated by Histone H3 Phosphorylation and Chromatin Structure

Osmotic Stress-dependent Repression Is Mediated by Histone H3 Phosphorylation and Chromatin Structure

Linking the ubiquitin–proteasome pathway to chromatin remodeling/modification by nuclear receptors

TATA box binding protein induces structure in the recombinant glucocorticoid receptor AF1 domain

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