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A functional glucocorticoid-responsive unit composed of two overlapping inactive receptor-binding sites: evidence for formation of a receptor tetramer. 总被引:1,自引:0,他引:1 下载免费PDF全文
M Garlatti M Daheshia E Slater J Bouguet J Hanoune M Beato R Barouki 《Molecular and cellular biology》1994,14(12):8007-8017
An unusual glucocorticoid-responsive element (called GRE A) was found to mediate the induction of the cytosolic aspartate aminotransferase gene by glucocorticoids and was bound by the glucocorticoid receptor in a DNase I footprinting assay. GRE A consists of two overlapping GREs, each comprising a conserved half-site and an imperfect half-site. The complete unit was able to confer glucocorticoid inducibility to a heterologous promoter (delta MTV-CAT). Mutation of any of the half-sites, including the imperfect ones, abolished inducibility by the hormone, demonstrating that each of the isolated GREs was inactive. In electrophoretic mobility shift assays, purified rat liver glucocorticoid receptor (GR) formed a low-mobility complex with GRE A, presumably containing a GR tetramer. When purified bacterially expressed DBD was used, low-mobility complexes as well as dimer and monomer complexes were formed. In inactive mutated oligonucleotides, no GR tetramer formation was detected. Modification of the imperfect half-sites in order to increase their affinity for GR gave a DNA sequence that bound a GR tetramer in a highly cooperative manner. This activated unit consisting of two overlapping consensus GREs mediated glucocorticoid induction with a higher efficiency than consensus GRE. 相似文献
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Mechanisms of glucocorticoid signalling 总被引:9,自引:0,他引:9
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We here demonstrated that the Soh1/MED31 protein is a stable component of Mediator complex isolated from Schizosaccharomyces pombe and Saccharomyces cerevisiae. Bioinformatic analysis traces the Soh1/MED31 family of Mediator subunits to the point of major eukaryotic divergence, before the appearance of the canonical heptapeptide repeat structure of the RNA polymerase II C-terminal domain. 相似文献
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