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 inappropriate production of the Evi-1 zinc finger protein occurs in retrovirus-induced murine myeloid leukemias and human acute myelogenous leukemias. In murine leukemias, expression of the Evi-1 gene is associated with retroviral insertions either in the Evi-1 locus, which is immediately 5' of the coding region of the gene, or in the genetically linked Cb-1/fim-3 locus. In these studies, we demonstrate by chromosomal walking and pulse field electrophoresis that the Cb-1/fim-3 locus is located 90 kb 5' of the Evi-1 locus. Primary structure analysis of Evi-1 cDNA clones from a Cb-1/fim-3 rearranged cell line (DA-3) demonstrates that transcription initiates 5' of the Evi-1 locus and that the first noncoding exon of the gene is 681 bp larger than previously defined. S1 nuclease protection studies reveal multiple transcription initiation sites within this region. Comparable transcriptional initiation sites were identified in RNA from kidney and ovary, in which the gene is normally expressed, suggesting that retroviral insertions in the Cb-1/fim-3 locus activate transcription from the normal promoter. In one myeloid cell line (DA-3), a single long terminal repeat (LTR) is present in the Cb-1/fim-3 locus. No stable transcripts were detectable from this LTR. In cells with retroviral insertions in the Cb-1/fim-3 locus, one allele of the Evi-1 locus becomes hypermethylated in the 5' region of the gene. Together, these results are most consistent with an LTR-mediated, long-range cis activation of Evi-1 gene expression.
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PMID:Retroviral insertions 90 kilobases proximal to the Evi-1 myeloid transforming gene activate transcription from the normal promoter. 184 63

Thrombopoietin (TPO) is predominantly expressed in the liver among various tissues that express TPO transcripts. To investigate the transcriptional regulation of the human TPO gene in the liver, we determined the major transcription initiation site by means of 5'-RACE and Northern blotting. From these analyses, we concluded that TPO gene transcription started at various points, and the transcription initiation sites of the human TPO gene were localized downstream, close to a point we determined by S1 nuclease mapping. The human TPO promoter region contains consensus sequences of GATA, Evi-1, and Ets binding sites. We used the hepatocellular carcinoma cell line, HepG2, that expresses TPO mRNA to analyze its promoter activity by transfecting various reporter plasmids containing a sequentially 5'-deleted human TPO promoter. Although GATA binding factors increased the promoter activity, their effect was independent of the GATA binding consensus sequence. On the other hand, Evi-1 did not affect transcription. Moreover, we defined the core promoter region, in which an Ets binding consensus sequence was located. The deletion or mutation of the Ets binding site resulted in a loss of the promoter activity. These results suggested that TPO is regulated by the Ets family of transcription factors.
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PMID:Gene expression and transcriptional regulation of thrombopoietin. 1101 15