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)

Structural analysis of the 5' end of the human c-fms gene revealed that a large intron of about 25 kilobases separates an upstream noncoding exon (exon 1) from the signal peptide-containing exon (exon 2). Northern (RNA) blot analysis, S1 nuclease mapping, and primer extensions showed that exon 1 is transcribed in placenta but not in cells of the monocytic lineage. This is due to the differential usage of promoters, separated by approximately 25 kilobases, in a cell-specific manner. One major c-fms transcript was observed in U-937 cells, whereas multiple initiation sites for transcription appeared to be utilized in placental cells. Nucleotide sequence comparisons showed that the 3' end of the human platelet-derived growth factor receptor gene lies approximately 350 base pairs upstream of the major initiation sites for c-fms transcription in placental trophoblasts.
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PMID:Differential transcription of exon 1 of the human c-fms gene in placental trophoblasts and monocytes. 252 48

To understand the mechanisms controlling platelet-derived growth factor receptor beta (PDGFR-beta) expression in malignancies, we have cloned and characterized the first functional promoter of the human PDGFR-beta gene, which has been confirmed by luciferase reporter gene assays. The transcription initiation sites were mapped by primer extension. Promoter deletion experiments demonstrate that the proximal, highly GC-rich region (positions -165 to -139) of the human PDGFR-beta promoter is crucial for basal promoter activity. This region is sensitive to S1 nuclease and likely to assume a non-B-form DNA secondary structure within the supercoiled plasmid. The G-rich strand in this region contains a series of runs of three or more guanines that can form multiple different G-quadruplex structures, which have been subsequently assessed by circular dichroism. A Taq polymerase stop assay has shown that three different G-quadruplex-interactive drugs can each selectively stabilize different G-quadruplex structures of the human PDGFR-beta promoter. However, in transfection experiments, only telomestatin significantly reduced the human PDGFR-beta basal promoter activity relative to the control. Furthermore, the PDGFR-beta mRNA level in Daoy cells was significantly decreased after treatment with 1 muM telomestatin for 24 h. Therefore, we propose that ligand-mediated stabilization of specific G-quadruplex structures in the human PDGFR-beta promoter can modulate its transcription.
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PMID:Molecular cloning of the human platelet-derived growth factor receptor beta (PDGFR-beta) promoter and drug targeting of the G-quadruplex-forming region to repress PDGFR-beta expression. 2037 8