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)

Transcription of the platelet-derived growth factor (PDGF) A-chain gene is activated in cells exposed to growth factors. We now have identified a homopurine/homopyrimidine domain in the promoter region of the PDGF A-chain gene that exhibits S1 nuclease sensitivity in vitro and that contains a novel binding site (5'-TCCTCCTCCTCCTC-3') for the growth factor inducible transcription factor EGR-1 as demonstrated in gel mobility shift assays. Sequences similar to this novel EGR-1 binding site were observed also in five growth-related genes and shown to bind to EGR-1 in competition assays, suggesting that EGR-1 may influence the transcriptional regulation of these growth-related genes.
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PMID:An S1 nuclease-sensitive homopurine/homopyrimidine domain in the PDGF A-chain promoter contains a novel binding site for the growth factor-inducible protein EGR-1. 141 65

Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a cell adhesion molecule involved in transendothelial migration and expressed by hemopoietic and endothelial cells. To understand the mechanisms underlying its regulated expression, a genomic clone containing 1555 bp of the 5'-flanking region and the first exon of the human PECAM-1 gene has been isolated. The 5'-flanking region of the PECAM-1 gene lacks a consensus TATA box, but contains consensus motifs for Sp1, EGR1, ets, helix-loop-helix (HLH) box, GATA, AP-2, C/EBP, YY1, CCACC, LyF-1, imperfect octamer, heptamer, high mobility group proteins (HMG) box, and nuclear factor-kappaB, as well as shear stress-, retinoic acid-, glucocorticoid-, and acute phase-responsive elements, and an Alu sequence. Successive 5' to 3' or 3' to 5' deletions revealed tissue-specific promoter activity within the two contiguous 0.22-kb NheI/BglII and 0.44-kb BglII/PstI fragments. The transcriptional activity displayed by the 0.22-kb NheI/BglII fragment was specific for the myeloid lineage, whereas the promoter activity of the 0.44-kb BglII/PstI fragment was apparently restricted to endothelial cells. The transcriptional activity of the 0.22-kb NheI/BglII fragment was confirmed by 5' RACE (rapid amplification of 5' cDNA ends) and S1 nuclease protection experiments that revealed previously unidentified transcription start sites. The 0.22-kb NheI/BglII promoter exhibited PMA inducibility in myeloid cells and contained a PMA-responsive element recognized by Sp1 and EGR-1 transcription factors. Isolation and characterization of the human PECAM-1 promoter represent an initial step in elucidating the controlled expression of the PECAM-1 gene.
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PMID:Cloning of the human platelet endothelial cell adhesion molecule-1 promoter and its tissue-specific expression. Structural and functional characterization. 895 89

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