Science · 2009 · 679 citations · 21 references
Life SciencesCell BiologyMolecular BiologyCell SignalingGene ExpressionTranscriptional RegulationAllosteric ModulationAllosteric RegulationHormone ReceptorsLigand BindingNuclear ReceptorsSteroid Hormone SignalingAllosteric Ligand BindingAllosteric Protein-ligand RecognitionCell-based AssaysDna Binding SitesGlucocorticoid ReceptorsGlucocorticoid SignalingReceptor Allosteric SitesSequence-specific Dna Binding
Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes are modulated so precisely is not well understood. The glucocorticoid receptor (GR) regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes. Traditionally, these binding sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR binding sequences, differing by as little as a single base pair, differentially affect GR conformation and regulatory activity. We therefore propose that DNA is a sequence-specific allosteric ligand of GR that tailors the activity of the receptor toward specific target genes.
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A signature motif in transcriptional co-activators mediates binding to nuclear receptors
David M. Heery, Eric Kalkhoven, Susan Hoare et al. · Nature · 1997 · 2.1K citations
Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA
Ben F. Luisi, Wei Xu, Zbyszek Otwinowski et al. · Nature · 1991 · 1.5K citations