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)

Cosmid clones containing the 5' region of the human alpha 2(VI) collagen gene have been isolated and characterized. DNA sequencing indicates that the signal peptide and the amino-globular domain are encoded by four exons of 142, 596, 21, and 66 base pairs (bp). However, S1 nuclease and primer extension analyses show that the transcription start site is not present in the 142-bp exon. Two different 5' cDNA clones are generated by the anchored polymerase chain reaction. Using the 5' cDNA clones as probes, two untranslated exons (1, 1A) are found 12 kilobase pairs upstream of the first coding exon. These two exons are alternatively used in human fibroblasts, and most transcripts contain exon 1 sequence. Exon 1 shows, by primer extension and S1 nuclease protection assay, two major and several minor transcription start sites. The promoter region contains a canonical TATA box, seven GGGCGG sequences, two possible CAAT boxes, and two sequences resembling AP2 binding sites. Exon 1A contains three alternative splice donor sites and is located 650 bp downstream of exon 1. The most 3' splice donor site of exon 1A is found within an Alu repeat sequence. Exon 1A is preceded by five GGGCGG sequences and one resembling the AP2 binding site although neither TATA or CAAT boxes are found. Two additional GGGCGG sequences are located at the beginning of exon 1A. This study establishes that the human alpha 2(VI) collagen gene is 36 kilobase pairs long and contains 30 exons. The 5'-untranslated and promoter regions are significantly different from the corresponding segments of the chicken gene. The human gene produces by alternative processing multiple mRNAs differing in the 5'-untranslated region as well as the 3'-coding and noncoding sequences.
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PMID:Human alpha 2(VI) collagen gene. Heterogeneity at the 5'-untranslated region generated by an alternate exon. 155 27

Genomic clones encompassing the human ETS1 gene were isolated and utilized to define its molecular organization. This gene consists of eight exons spanning over 60 kb. The 5' end of the human ETS1 gene was subcloned and characterized. S1 nuclease, primer extension and RNAase protection analyses of human mRNAs showed multiple transcription initiation sites. DNA sequence analysis indicated a high G + C content in the promoter region and the absence of either a 'TATA' box or a 'CAAT' box. Six consensus recognition sequences for the transcription factor SP1, two AP1 consensus sequences and one consensus AP2 recognition sequence were identified, as well as two GC elements with dyad symmetry. A palindromic region similar to the serum response element of the c-fos gene and two octamer consensus recognition sequences were located upstream of the promoter region. A series of promoter deletion constructs positioned upstream from the bacterial chloramphenicol acetyl transferase gene were transfected into HeLa cells and their functional promoter activity assayed. The deletion constructs identified the 5' boundary for maximum promoter activity at 486 bp upstream of the first initiation site and suggest possible positive and negative regulatory regions. Polymerase chain reaction analysis of ETS1 cDNA identified several amplified products, indicating alternative splicing. In addition to the presence of mRNA products lacking exon VII, products lacking exon IV, as well as ones lacking both exons IV and VII, were found.
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PMID:The human ETS1 gene: genomic structure, promoter characterization and alternative splicing. 203 Sep 10

We identified a transcription unit within a single exon of the rat insulin like growth factor II (rIGFII) gene by a combination of Northern blotting, S1 nuclease mapping and primer extension analyses. Among multiple mRNA products of rIGFII, the 1.8kb transcript has a discrete 5' terminus and is encoded exclusively in a single 3'-extreme exon with no trace of the coding region. The upstream region of the 5' terminus contains a completely matching GC-rich 16bp palindrome and several sequence motifs highly homologous to the consensus sequences of binding sites for transcriptional regulatory proteins AP2, H2TF1 and NF-kappa B.
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PMID:A novel transcription unit within the exon sequence of the rat insulin like growth factor II gene. 271 15

Genomic clones encompassing the entire human elastin gene, including 11 kilobases flanking the ATG translation initiation codon, have been obtained and characterized by restriction enzyme analysis and extensive DNA sequencing. These analyses demonstrated that functionally distinct hydrophobic and cross-linking domains of the protein are segregated into separate exons throughout the gene. All exons are multiples of three nucleotides, and exon:intron borders always split codons in the same way which permits cassette-like alternative splicing. The 5'-flanking region lacks a canonical TATA sequence, is G + C-rich, and contains several SP1 binding sites and an AP2 binding site. Primer extension and S1 nuclease protection experiments indicate that transcription is initiated at multiple sites in the gene.
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PMID:Characterization of the complete human elastin gene. Delineation of unusual features in the 5'-flanking region. 272 4

Synapsin II is an abundant peripheral membrane protein of synaptic vesicles that is expressed exclusively in neuronal cells. Here we report the isolation and characterization of the 5'-terminal region of the murine synapsin II gene. Primer extension and S1 nuclease protection analysis show that synapsin II gene transcription is initiated from a unique site. The synapsin II gene promoter contains no canonical TATA or CAAT boxes but has putative binding sites for the transcription factors Sp1, AP2, and NGFIA. This promoter is embedded in a large G+C-rich domain with characteristics of a CpG island. Transfection experiments using synapsin II-luciferase fusion genes demonstrate that the 5'-flanking sequence functions as a strong promoter in neuronal but not in nonneuronal cells. Deletion analysis reveals the presence of a neuron-specific core promoter (-79 to 153) and, upstream, two positive and one negative regulatory elements. The 5'-terminal region of the murine synapsin I gene was also cloned and sequenced. Although there is no extensive sequence homology between the 5'-flanking regions of the synapsin I and II genes, comparison analysis has identified two regions of homologous sequences, which may be involved in determining neuron specificity of the core promoters of these two genes.
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PMID:Neuron-specific expression of the synapsin II gene is directed by a specific core promoter and upstream regulatory elements. 803 99

Histidase (EC 4.3.1.3) is a cytosolic enzyme that catalyzes the nonoxidative deamination of histidine to urocanic acid. Histidinemia, resulting from reduced histidase activity as reported in Cambridge stock his/his mice and in humans, is the most frequent inborn metabolic error in Japan. The histidase chromosomal gene (HAL) was isolated from a lambda EMBL-3 human genomic library using the human histidase cDNA as a probe. Restriction mapping and Southern blot analysis of the isolated clones reveal a single-copy gene spanning approximately 25 kb and consisting of 21 exons. Exon 1 encodes only 5' untranslated sequence of liver histidase mRNA, with protein coding beginning in exon 2. A rarely observed 5' GC, similar to that reported in the human P-450 (SCC) gene, is present in intron 20. All other splicing junctions adhere to the canonical GT/AG rule. A TATA box sequence is located 25 bp upstream of the liver histidase transcription initiation site determined by S1 nuclease protection analysis. Several liver- and epidermis-specific transcription factor binding sites, including C/EBP, NFIL6, HNF5, AP2/KER1, MNF, and others, are also identified in the 5' flanking region. Consistent with the hepatic and epidermal expression of histidase, this finding suggests that histidase transcription may be regulated by these factors. We further identify a polymorphism (A to G transition) in the histidase coding region of exon 16. The human histidase genomic structure presented here should facilitate the molecular investigation of symptomatic and asymptomatic forms of histidinemia.
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PMID:Molecular cloning and structural characterization of the human histidase gene (HAL). 853 Jan 7

In this study the gene for the murine interleukin-11 receptor alpha chain (IL-11Ralpha) has been characterized. The gene spans 9 kilobase pairs of DNA, and the organization of its 14 exons conforms to the pattern observed for other members of the hematopoietin receptor family. Analysis of the 5' end of the cDNA using 5' RACE showed that the first two exons, designated exons 1a and 1b, are spliced to form alternate transcripts. Transcripts initiating from exon 1b were not found in adult tissues but were present in embryonic stem cells. S1 nuclease and 5' rapid amplification of cDNA ends assays demonstrated multiple major and minor sites of transcription initiation for each exon. The putative promoter regions of both exons lacked TATA boxes, although potential recognition sites for several transcription factors including Sp1, AP1, and AP2 were present. A comparison of the murine and human IL-11Ralpha revealed that the 5' sequence upstream of the major site of transcription initiation site for exon 1b is highly conserved. Northern analysis showed that IL-11Ralpha is expressed in many adult murine tissues. A second IL-11Ralpha-like locus containing a sequence homologous to exons 2-13 was also identified.
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PMID:Structural analysis of the gene encoding the murine interleukin-11 receptor alpha-chain and a related locus. 866 2

The human ATP1AL1 gene belongs to the family of Na,K-ATPase and H,K-ATPase (X,K-ATPases) genes. It encodes a catalytic subunit of hitherto unknown human ouabain-sensitive H,K-ATPase that represents a novel third group of X,K-ATPases distinct from the known Na,K-ATPase and gastric H,K-ATPase. Cloning of the ATP1AL1 gene is described in this report. The exon-intron structure of ATP1AL1 was found to be very similar to that of related genes. It contains 23 exons and spans approximately 32 kb of genomic DNA. All ATP1AL1 exons and 12 of its 22 introns were entirely sequenced. A total of nine Alu repeats were identified in introns. The transcription initiation site was mapped 187 bp upstream of the ATG initiation codon by primer extension and S1 nuclease protection analyses of RNA from human skin and colon. Sequence analysis of the 5'-flanking region (1.48 kb) revealed numerous potential binding sites for transcription factors Sp1 and AP2 and one putative NF-kappa B binding site. The 0.85-kb region from position -484 (5'-flanking region) to position +369 (intron 1) meets the structural criteria of a CpG island. It is suggested that the ATP1AL1 gene contains two poly(A) addition sites that may function in a tissue-specific manner.
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PMID:Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase. 883 94

Expression of human estrogen receptor-alpha (ERalpha) involves the activity from several promoters that give rise to alternate untranslated 5' exons. However, the genomic locations of the alternate 5' exons have not been reported previously. We have developed a contig map of the human ERalpha gene that includes all of the known alternate 5' exons. By using S1 nuclease and 5'- rapid amplification of cDNA ends, the cap sites for the alternate ERalpha transcripts E and H were identified. DNase I-hypersensitive sites specific to ERalpha-positive cells were associated with each of the cap sites. A DNase I-hypersensitive site, HS1, was localized to binding sites for AP2 in the untranslated region of exon 1 and was invariably present in the chromatin structure of ERalpha-positive cells. Overexpression of AP2gamma in human mammary epithelial cells generated the HS1-hypersensitive site. The ERalpha promoter was induced by AP2gamma in mammary epithelial cells, and trans-activation was dependent upon the region of the promoter containing the HS1 site. These results demonstrate that AP2gamma trans-activates the ERalpha gene in hormone-responsive tumors by inducing changes in the chromatin structure of the ERalpha promoter. These data are further evidence for a critical role for AP2 in the oncogenesis of hormone-responsive breast cancers.
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PMID:Genomic structure of the promoters of the human estrogen receptor-alpha gene demonstrate changes in chromatin structure induced by AP2gamma. 1127 55