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

We mapped and sequenced three upstream exons of the chicken c-myb gene and the regions flanking the first coding exon. We found multiple potential binding sites for transcription factors in the 5'-noncoding region, a T-rich stretch of 78 base pairs (bp) (68% T) in the first intron, and four fairly long open reading frames in the antisense direction of the first coding exon and its flanking regions. Three major transcription start sites, contained within a single 11-bp region, were identified by S1 nuclease analysis and primer extension. A sequence comparison of the avian and murine c-myb genes revealed a highly conserved sequence of 124 bp in the 5'-noncoding region. Its location between the putative transcription factor binding sites and the major transcription start sites suggests that it may play an important regulatory role in c-myb expression.
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PMID:Structural organization of upstream exons and distribution of transcription start sites in the chicken c-myb gene. 271 Jan 26

BldD is a transcription factor required for aerial hyphae formation in the filamentous bacterium Streptomyces coelicolor. Three targets of BldD regulation were discovered by a number of means, including examination of bld gene interdependence, selective enrichment of chromosomal DNA fragments bound by BldD and searching the promoter regions of known developmental genes for matches to a previously characterized BldD binding site. The three BldD targets identified were the developmental sigma factor genes, whiG and bldN, and a previously uncharacterized gene, designated bdtA, encoding a putative transcription factor. In each target gene, the sequences bound by BldD were characterized by electrophoretic mobility shift and DNase I footprinting assays, and their alignment suggested AGTgA (n)m TCACc as a consensus BldD operator. The in vivo effect of mutation in bldD on the expression of these three target genes was assessed using S1 nuclease protection assays. In each case, target gene expression was upregulated during early colony development in the bldD background, suggesting that, in the wild type, BldD acts to repress premature expression of whiG, bldN and bdtA during vegetative growth.
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PMID:BldD is a direct regulator of key developmental genes in Streptomyces coelicolor A3(2). 1129 92

We previously reported on the isolation of a new rat ATP binding cassette (ABC) transporter, ABCB6. We now report the isolation of the full-length cDNA and genomic clones containing the human ABCB6 gene. ABCB6 is 100% identical to the cloned MTABC3 human ABC transporter and contains the typical ABC signature, Walker A and B motifs. We found that HuABCB6 is expressed at low levels in normal human liver. We found that ABCB6 was overexpressed in human hepatocellular carcinomas compared to paired surrounding non-malignant tissue. We found that there was no difference in ABCB6 gene copy between human liver cancer and its paired non-malignant tissue. Because HuABCB6 was overexpressed in human cancers compared to peri-tumoral tissue in the absence of gene amplification, transcriptional regulation may play an important role in its expression. Therefore, we isolated a 14 kb genomic DNA clone containing the HuABCB6 promoter and 5'-flanking region. The 5'-flanking region contains a CpG island, lacks an appropriately positioned TATA element and contains a number of putative transcription factor binding sites. Two transcription start sites were identified by S1 nuclease mapping at -274 and -296 bp from the start codon. Transient transfection of the HuABCB6 promoter constructs (HuABCB6/1.68, 1.39, 1.13, 0.90, 0.52) containing the luciferase reporter gene resulted in a 1100-2300-fold increase in luciferase activity compared to the empty vector control whereas HuABCB6/1.68 subcloned in the reverse orientation resulted in no activity. We observed a significant decrease in luciferase activity with the promoter constructs, HuABCB6/0.25, 0.15 and 0.06, which indicates that an orientation-dependent functional promoter is contained within our previously predicted promoter region of -315 bp to -565 bp as deletion of this 250 bp sequence resulted in a loss of promoter activity.
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PMID:Isolation of a genomic clone containing the promoter region of the human ATP binding cassette (ABC) transporter, ABCB6. 1195 20