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

Steroids regulate alternative splicing of RUSH/SMARCA3. The full-length, progesterone-dependent alpha-isoform and the 3'-truncated, estrogen-dependent beta-isoform have identical DNA-binding domains, nuclear localization signals, and RING fingers. Transcription of RUSH/SMARCA3 is mediated by a bipartite progesterone receptor half-site/overlapping Y-box combination (-38/-26), where progesterone activation is attenuated by nuclear factor Y binding. Regulation also involves two GC-rich sequences in the proximal promoter (-162/+90) and a RUSH/SMARCA3 site (-616/-611) in the 5'-untranslated region. Isoform-specific binding to the RUSH/SMARCA3 site is dictated by the hormonal milieu, as is the availability of factors that bind to the distal GC-rich site (-131/-126), a composite binding site for Egr-1/specific protein-1/3/Myc-associated zinc finger protein/myeloid zinc finger-1/c-Rel, and the proximal GC-rich site (-62/-53), which binds only Sp1/3. TransSignal TF-TF interaction arrays, supershift assays, and chromatin immunoprecipitation analyses confirmed strong physical interactions between RUSH/Egr-1 and RUSH/c-Rel that were visualized with fluorescent microscopy. Higher-order, long-range interactions between RUSH and Egr-1/c-Rel derivative of the anisotropic flexibility of the intervening DNA sequence were shown by Chromosome Conformation Capture assay. Glutathione S-transferase pull-downs confirmed that the RING finger is the protein-binding domain, suggesting that the RUSH isoforms have equivalent potential for protein interactions. Transient transfection assays showed that the cooperative interaction between RUSH and Egr-1 mediates repression by c-Rel. Thus, progesterone-induced transcription is fine-tuned by isoform-specific autoregulation, in which newly synthesized RUSH-1alpha binds DNA and interacts physically with liganded Egr-1 in the proximal promoter via a DNA-looping mechanism to mediate repression by c-Rel. In the absence of progesterone induction, RUSH-1beta replaces RUSH-1alpha binding, Egr-1 and c-Rel are unavailable as molecular ties, and DNA looping is disfavored.
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PMID:Progesterone-dependent deoxyribonucleic acid looping between RUSH/SMARCA3 and Egr-1 mediates repression by c-Rel. 1817 57