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)

We have isolated and analyzed the structure of the gene for thymidylate synthase from a 5-fluoro-2'-deoxyuridine-resistant 3T6 cell line that overproduces thymidylate synthase 50-fold by virtue of gene amplification. Three overlapping DNA segments containing the entire thymidylate synthase gene were identified in Charon 35 genomic libraries. Sequence analysis revealed that all of the coding regions were contained in a 12-kilobase segment of DNA. The gene has 6 introns ranging from 0.6 to 4.1 kilobases in length. The sequences at the 5' and 3' ends of each intron conformed to the consensus sequences for mammalian introns. S1 nuclease and primer extension assays showed that transcription of the thymidylate synthase gene initiates at several sites within a 66-nucleotide region. There are no TATAA or CCAAT sequences in the vicinity of the initiation sites. However, the region does contain DNA sequences that are known to stimulate binding of the transcription factors Sp1 and USF. These binding sites are adjacent to each other, suggesting that the two proteins may bind to the upstream region of the thymidylate synthase gene in a cooperative or competitive manner.
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PMID:Structure of the gene for mouse thymidylate synthase. Locations of introns and multiple transcriptional start sites. 378 3

Upstream stimulatory factors (USF/MLTF) belong to the c-myc family of transcription factors. Through binding to target DNA as dimers, the ubiquitous USF proteins regulate a variety of genes. USF proteins are encoded by two genes, USF1 and USF2. Protein sequences of USF1 and 2 are highly homologous across species, suggesting functional conservation. To determine whether the genomic organization was conserved between USF1 and USF2, we isolated the murine USF1 gene and characterized its genomic structure. Both genes are similarly organized in 10 exons spanning over 10 kbp. By the 5'-rapid amplification of cDNA ends and S1 nuclease mapping methods, exon 1 was defined and the transcription initiation sites were mapped. The sequence of 8 kb of the gene, including 1.75 kb of 5'-flanking DNA, was determined. The promoter region is GC rich and lacks a typical TATA or CCAAT element. Strikingly, a comparison of the murine and human untranslated sequences reveals regions that exhibit greater than 73% sequence identity. A genomic alignment of the dimerization and DNA binding domains is presented for five genes of the c-myc family, suggesting a hypothetical common ancestor gene.
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PMID:Mouse USF1 gene cloning: comparative organization within the c-myc gene family. 887 87

In this study, an endogenous factor(s) involved in the suppression of the induction of CYP1A1 was studied. Analyzing the sequences, we found that the sequence of xenobiotic responsive element (XRE) in the upstream region of the human CYP1A1 gene was overlapped with that of the upstream stimulatory factor 1 (USF1)-binding site in mouse metallothionein I promoter. In fact, a gel shift assay using a specific competitor or mutant probes showed that the core sequence of human XRE was specifically recognized by USF1. The amount of USF1 in the nuclear extracts from HepG2 cells was smaller than that from rat and rabbit livers as assayed by the binding to XRE. To determine whether or not USF1 could inhibit the interaction of aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (Arnt) complex with XRE, we transfected USF1-SR alpha expression vector into HepG2 cells. The results showed that no interaction of AhR/Arnt complex with XRE occurred even when the cells were treated with 2,3,7,8-tetrachlorodibenzofuran (TCDF). Furthermore, the S1 nuclease protection assay showed that the induction of CYP1A1 mRNA by 3-methylcholanthrene (MC) was depressed by the transfection of USF1-SR alpha into HepG2 cells. Thus, it is highly possible that USF1 negatively regulates the induction of CYP1A1 in humans.
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PMID:Upstream stimulatory factor 1 (USF1) suppresses induction of CYP1A1 mRNA by 3-methylcholanthrene (MC) in HepG2 cells. 938 70