Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Steroids regulate alternative splicing of rabbit RUSH/SMARCA3, an SWI/SNF-related transcription factor. Transactivation was evaluated in 2057 bp of genomic sequence. Truncation analysis identified a minimal 252-bp region with strong basal promoter activity in transient transfection assays. The size of the 5'-untranslated region (233 bp) and the transcription start site were determined by primer extension analysis. The transcription start site mapped to a consensus initiator (Inr) element in a TATA-less region with a downstream promoter element (+29). These elements were authenticated by mutation/deletion analysis. The Inr/downstream promoter element combination is conserved in the putative core promoter (-35/+35) of the human ortholog, suggesting that transcription initiation is similarly conserved. Two Sp1 sites that are also conserved in the putative promoter of human SMARCA3 and a RUSH binding site (-616/-611) that is unique to the rabbit promoter repress basal transcription. These sites were variously authenticated by gel shift and chromatin immunoprecipitation assays. Analysis of the proximal promoter showed the -162/+90 region was required for progesterone responsiveness in transient transfection assays. Subsequent mutation/deletion analysis revealed a progesterone receptor half-site mediated induction by progesterone. An overlapping Y-box (in the reverse ATTGG orientation) repressed basal transcription and progesterone-induced transcriptional activation in the presence of the Sp1 sites. The specificity of progesterone receptor and transcription factor NF-Y binding were authenticated by gel shift assays. Chromatin immunoprecipitation assays confirmed the Y-box effects were mediated in a DNA binding-dependent fashion. This represents a unique regulatory scenario in which ligand-dependent transactivation by the progesterone receptor is subject to Sp1/NF-Y repression.
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PMID:An Sp1-NF-Y/progesterone receptor DNA binding-dependent mechanism regulates progesterone-induced transcriptional activation of the rabbit RUSH/SMARCA3 gene. 1289 Jun 80

Antiprogestin-controlled gene regulation systems, initially developed by Bert O'Malley and colleagues, are based on the unusual properties of certain truncated progesterone receptor ligand-binding domains (PR-LBDdelta19). These modified PR-LBDs have lost the ability to respond to progestins, but have gained the ability to respond to antiprogestins as agonists, rather than as antagonists. When a modified PR-LBD is joined to specific DNA-binding and transcription activator domains, the resultant chimeric protein functions as an antiprogestin-inducible transcription factor for transgenes linked to promoters with specific DNA-binding sites. Antiprogestin-inducible gene regulation systems have been used to regulate transgene expression in cultured cells, transgenic animals, and for in vivo gene transfer studies using viral- or plasmid-based vectors. We have designed a plasmid-based, muscle-specific GeneSwitch system that is delivered to skeletal muscle by electroporation and provides regulated erythropoietin (EPO) expression in mice and rats in a manner that is dependent on orally administered mifepristone (MFP). Regulation was effective at low doses of MFP and provided regulated biological responses (hematocrit changes) for more than 6 months. This plasmid-based, antiprogestin-inducible EPO/GeneSwitch system has the potential to be a convenient, long-lasting and effective gene-based therapy for the treatment of anemia.
Steroids 2003 Nov
PMID:The antiprogestin-dependent GeneSwitch system for regulated gene therapy. 1466 2