Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Wilms' tumor gene WT1 is a recessive oncogene that encodes a putative transcription factor implicated in nephrogenesis during kidney development. In this report we analyze expression of WT1 in the murine urogenital system. WT1 is expressed in non-germ-cell components of the testis and ovaries in both young and adult mice. In situ mRNA hybridization studies demonstrate that WT1 is expressed in the granulosa and epithelial cells of ovaries, the Sertoli cells of the testis, and in the uterine wall. In addition to the 3.1-kb WT1 transcript detected by Northern blotting of RNA from kidney, uterus, and gonads, there is an approximately 2.5-kb WT1-related mRNA species in testis. The levels of WT1 mRNA in the gonads are among the highest observed, surpassing amounts detected in the embryonic kidney. During development, these levels are differentially regulated, depending on the sexual differentiation of the gonad. Expression of WT1 mRNA in the female reproductive system does not fluctuate significantly from days 4 to 40 postpartum. In contrast, WT1 mRNA levels in the tesis increase steadily after birth, reaching their highest expression levels at day 8 postpartum and decreasing slightly as the animal matures. Expression of WT1 in the gonads is detectable as early as 12.5 days postcoitum (p.c.). As an initial step toward exploring the tissue-specific expression of WT1, DNA elements upstream of WT1 were cloned and sequenced. Three putative transcription initiation sites, utilized in testis, ovaries, and uterus, were mapped by S1 nuclease protection assays. The sequences surrounding these sites have a high G + C content, and typical upstream CCAAT and TATAA boxes are not present. These studies allowed us to identify the translation initiation site for WT1 protein synthesis. We have also used an epitope-tagging protocol to demonstrate that WT1 is a nuclear protein, consistent with its role as a transcription factor. Our results demonstrate regulation of WT1 expression during development of the gonads, implicate WT1 in genitourinary development, and provide a molecular framework toward understanding genitourinary defects observed among hereditary cases of Wilms' tumor.
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PMID:Expression of the Wilms' tumor gene WT1 in the murine urogenital system. 165 Dec 75

Transcription of the PDGF-A chain gene is regulated by multiple promoter and silencer elements that are GC-rich and exhibit considerable single-stranded character. In this study, the 42 kDa single-stranded DNA and RNA binding protein, Puralpha, was investigated with respect to its ability to bind and interact functionally with single-stranded DNA elements in the PDGF-A gene. Recombinant GST-Puralpha bound with high affinity and sequence-specificity to the G-rich strands of two such transcriptional control elements, the 5'-S1 nuclease-hypersensitive silencer (5'SHS; -1418 to -1388) and the nuclease-hypersensitive element (NHE; -92 to -48). Ethylation interference footprinting localized binding of Puralpha to a region between nucleotides -91 and -77 within the NHE element, which contains binding sites for the double-stranded DNA-binding transcription factors Sp1, EGR-1 and WT1. Forced expression of Puralpha upregulated transcriptional activity of the PDGF-A promoter but not the 5'SHS silencer in HepG2 cells, demonstrating Puralpha has the potential to activate PDGF-A gene expression. Targeted disruption of the Puralpha gene reduced NHE activity and PDGF-A mRNA expression in mouse embryo fibroblasts, consistent with a physiological role for Puralpha in maintaining optimal transcription of the PDGF-A gene. These results indicate Puralpha enhances transcription of the PDGF-A gene through its interactions with single-stranded, G-rich strands in the promoter, perhaps by stabilizing non-B-form DNA conformations.
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PMID:Puralpha activates PDGF-A gene transcription via interactions with a G-rich, single-stranded region of the promoter. 1577 9