Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To analyze the mechanism of the cell type-specific expression of protein kinase C beta (PKC beta), we isolated the 5'-portion of the human gene for PKC beta and identified multiple positive and negative regulatory sequences that regulate its transcription. S1 nuclease mapping as well as primer extension analysis of the 5'-end of the PKC beta mRNA identified a putative transcriptional initiation site (position +1) 484 base pairs (bp) upstream of the first ATG codon. The 5'-upstream sequence contains a CCAAT sequence at position -110, but no TATA box. The transcriptional activities of various 5'-deletion mutants of the PKC beta gene upstream region, fused to the chloramphenicol acetyltransferase structural gene, were examined in terms of chloramphenicol acetyltransferase expression after transfection into three kinds of rodent cell lines: P19 and GH4C1, which are positive for the expression of PKC beta mRNA; and 3Y1, which is negative. Mutants containing a 5'-flanking sequence longer than 1.9 kilobases (kb) showed chloramphenicol acetyltransferase activities of the same order as the expression of the endogenous gene. This indicates that this region contains sequences regulating the cell-type specificity of PKC beta gene expression and that the specificity is determined at least partially at the level of transcription. The 1.9-kb sequence contains at least three positive elements: P1 (-56 to -234 bp), P2 (-234 to -411 bp), and PN (-1.4 to -1.9 kb). PN is active only in P19 cells, P1 in GH4C1 and P19 cells, and P2 in all three cell lines. In addition to these positive elements, there are negative elements: N1 (-411 to -674 bp), which is active in all three cell lines; and PN, which is active only in GH4C1 cells. These results suggest the presence of multiple trans-acting factors that act on these positive and negative cis-acting elements and regulate the cell type-specific expression of the PKC beta gene.
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PMID:Positive and negative regulation of the transcription of the human protein kinase C beta gene. 155 24

The mouse ST8Sia II (mST8Sia II/STX) gene encodes a neural cell adhesion molecule-specific polysialic acid synthase whose expression is regulated during the developmental stages of mouse brain. To elucidate the molecular mechanism by which the expression is tissue-specifically and developmentally regulated, we isolated the complete genomic DNA and characterized the promoter of the gene for mST8Sia II. The gene encoding mST8Sia II was found to span about 80 kilobases and to be composed of six exons. Primer extension and S1 nuclease protection analyses revealed that the transcription started from 167 nucleotides upstream of the translational initiation site. Promoter analyses of the 5'-flanking region of the mST8Sia II gene using a luciferase gene reporter system revealed strong promoter activity in retinoic acid-induced differentiated P19 cells, which highly express the mST8Sia II gene. Deletion analyses demonstrated that the minimal promoter activity detected for the proximal region 325 base pairs upstream from the translational initiation codon (-158 to +167) could be modulated by various sequences within the 9. 5-kilobase 5'-flanking region. The minimal promoter was embedded in a GC-rich domain (74%, GC content), in which two Sp1 binding motifs as well as a long purine-rich region were found, but it lacked TATA and CAAT boxes. The positive regulatory region located between -159 and -659 contained two additional Sp1 binding motifs and a long pyrimidine-rich region. We also found that the minimal promoter region of the mST8Sia II gene was sufficient for expression of a reporter gene in mST8Sia II gene-expressing neural differentiated P19 cells but not in nonexpressing ones. Thus the TATA-less GC-rich minimal promoter region of mST8Sia II probably controls the cell type-specific expression of the mST8Sia II gene.
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PMID:Genomic structure and promoter activity of the mouse polysialic acid synthase gene (mST8Sia II). Brain-specific expression from a TATA-less GC-rich sequence. 893 67

ERK2 (extracellular-signal regulated kinase 2, also known as p42 mitogen-activated protein kinase) is an integral member of the mitogen-activated protein kinase cascade that is crucial for many cellular events such as proliferation and differentiation. Here, we determined the genomic organization of the Erk2 gene and characterized its promoter. The Erk2 gene spans over 60 kilobases, and the coding region is split into eight exons. In the coding region, exon-intron organization was exactly conserved between the two mouse genes for ERK2 and ERK1 except one junction shifted by one nucleotide. Primer extension and S1 nuclease analyses identified two major transcription start sites located at -219 and -223 relative to the translation start site. The 5'-flanking sequence lacked TATA box but contained a CCAAT box located approximately 60 base pairs upstream of transcription start sites. Sequencing of the 5'-flanking region also revealed potential cis-acting elements for multiple transcriptional regulatory factors including Sp1, zif268, Ets, CREB, and PuF sites. The promoter activity of the 5'-flanking region was examined using chloramphenicol acetyltransferase as a reporter gene. Transient transfection experiments using Chinese hamster ovary cells defined a maximal promoter activity in a 371-base pair region immediately upstream of the translation start site. Furthermore, we demonstrated, using mouse P19 embryonal carcinoma cells, that this 371-base pair sequence is likely to be sufficient to confer the transcriptional activation of the ERK2 promoter during the retinoic acid-induced differentiation of P19 cells.
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PMID:The mouse extracellular signal-regulated kinase 2 gene. Gene structure and characterization of the promoter. 926 Nov 78