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Biochemistry
2006 Jun 13;4523:7299-306. doi: 10.1021/bi060314k.
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Flanking sequence composition differentially affects the binding and functional characteristics of glucocorticoid receptor homo- and heterodimers.
Morin B
,
Nichols LA
,
Holland LJ
.
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The core binding sites for a multitude of transcription factors have been identified and characterized, but these sequences cannot fully account for the nuances of cell-specific and gene-specific control of gene transcription. Many factors may contribute to the precise responsiveness of a gene to a particular transcriptional regulatory protein, including the nucleotides in the proximity of the core binding site for that protein. Here, we examine two flanking sequences bordering a site in the gamma-fibrinogen gene regulatory region that binds a heterodimer of the Xenopus glucocorticoid receptor accessory factor (XGRAF) and the glucocorticoid receptor (GR). Mutation of the upstream flank results in a decrease in the level of XGRAF binding but little change in hormone induction. However, alteration of the downstream flank adjacent to the GR binding site causes a decrease in levels of both GR monomer binding and hormone induction. Conversion of the XGRAF-GR binding site to a full glucocorticoid response element (GRE) alters the role of the flanking sequences. A full GRE in this position requires the wild-type upstream flank to bind GR homodimer and induce transcription to maximal levels. In contrast, mutation of the downstream flank is not detrimental to either the binding or the function of the GR dimer. Thus, flanking sequence composition and dimer partner combine to influence GR function, underscoring the complexities involved in the identification of authentic transcription factor response elements.
Aumais,
Function of directly repeated half-sites as response elements for steroid hormone receptors.
1996, Pubmed
Aumais,
Function of directly repeated half-sites as response elements for steroid hormone receptors.
1996,
Pubmed
Beato,
DNA regulatory elements for steroid hormones.
1989,
Pubmed
,
Xenbase
Connor,
Sequences flanking the cAMP responsive core of the HTLV-I tax response elements influence CREB protease sensitivity.
2000,
Pubmed
Freedman,
The function and structure of the metal coordination sites within the glucocorticoid receptor DNA binding domain.
1988,
Pubmed
,
Xenbase
Gaunitz,
A silencer element in the first intron of the glutamine synthetase gene represses induction by glucocorticoids.
2004,
Pubmed
Hallikas,
Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity.
2006,
Pubmed
Holland,
Xenopus liver ferritin H subunit: cDNA sequence and mRNA production in the liver following estrogen treatment.
1991,
Pubmed
,
Xenbase
Kato,
Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers for different classes of nuclear receptors.
1995,
Pubmed
Kelly,
A pair of adjacent glucocorticoid response elements regulate expression of two mouse metallothionein genes.
1997,
Pubmed
Ki,
Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression.
2005,
Pubmed
La Baer,
Analysis of the DNA-binding affinity, sequence specificity and context dependence of the glucocorticoid receptor zinc finger region.
1994,
Pubmed
Lefstin,
Allosteric effects of DNA on transcriptional regulators.
1998,
Pubmed
Leung,
One nucleotide in a kappaB site can determine cofactor specificity for NF-kappaB dimers.
2004,
Pubmed
Li,
Analysis of the DNA-binding site for Xenopus glucocorticoid receptor accessory factor. Critical nucleotides for binding specificity in vitro and for amplification of steroid-induced fibrinogen gene transcription.
1998,
Pubmed
,
Xenbase
Mangelsdorf,
The RXR heterodimers and orphan receptors.
1995,
Pubmed
Morin,
Heterodimerization between the glucocorticoid receptor and the unrelated DNA-binding protein, Xenopus glucocorticoid receptor accessory factor.
2001,
Pubmed
,
Xenbase
Morin,
The binding site for Xenopus glucocorticoid receptor accessory factor and a single adjacent half-GRE form an independent glucocorticoid response unit.
2000,
Pubmed
,
Xenbase
Mullick,
Physical interaction and functional synergy between glucocorticoid receptor and Ets2 proteins for transcription activation of the rat cytochrome P-450c27 promoter.
2001,
Pubmed
Natoli,
Little things that count in transcriptional regulation.
2004,
Pubmed
Nordeen,
Structural determinants of a glucocorticoid receptor recognition element.
1990,
Pubmed
Nordeen,
Extreme position dependence of a canonical hormone response element.
1998,
Pubmed
Roberts,
Transcriptional regulation of the Xenopus laevis B beta fibrinogen subunit gene by glucocorticoids and hepatocyte nuclear factor 1: analysis by transfection into primary liver cells.
1993,
Pubmed
,
Xenbase
Sandelin,
Prediction of nuclear hormone receptor response elements.
2005,
Pubmed
Srinivasan,
Overexpression of full-length human glucocorticoid receptor in Spodoptera frugiperda cells using the baculovirus expression vector system.
1990,
Pubmed
Stafford,
Accessory factors facilitate the binding of glucocorticoid receptor to the phosphoenolpyruvate carboxykinase gene promoter.
2001,
Pubmed
Stormo,
DNA binding sites: representation and discovery.
2000,
Pubmed
Tsai,
Molecular interactions of steroid hormone receptor with its enhancer element: evidence for receptor dimer formation.
1988,
Pubmed
Wasserman,
Applied bioinformatics for the identification of regulatory elements.
2004,
Pubmed
Winter,
A hormone response element upstream from the human alcohol dehydrogenase gene ADH2 consists of three tandem glucocorticoid receptor binding sites.
1990,
Pubmed
Woodward,
Novel accessory factor-binding site required for glucocorticoid regulation of the gamma-fibrinogen subunit gene from Xenopus laevis.
1997,
Pubmed
,
Xenbase
d'Emden,
Analysis of functional cooperativity between individual transcription-stimulating elements in the proximal region of the rat prolactin gene.
1992,
Pubmed
