Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.21.1 (DNase)
7,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human c-fps/fes proto-oncogene is expressed as a transcript of about 3.0 kb in both normal and leukemic myeloid cells. We have detected truncated c-fps/fes transcripts of about 0.9 kb in a panel of human lymphoma and lymphoid leukemia cell lines, but not in normal untransformed hematopoietic cells. Analysis of the chromatin structure of the c-fps/fes gene revealed DNAase I-hypersensitive sites in the 5' region of the gene and in exon 16. The presence and absence of these sites correlates with the expression of the 3.0 kb and 0.9 kb c-fps/fes RNAs respectively. The truncated transcripts initiate at two distinct sites within exon 16 of the c-fps/fes gene. The genomic region 5' to the transcription initiation sites is G+C rich but does not contain typical promoter consensus sequences. Sequence analysis of a cDNA clone of the truncated c-fps/fes transcripts did not reveal any point mutation and the truncated transcripts are normally spliced using the regular splice donor and acceptor sites. A putative open reading frame encompasses the phosphotransfer motif and the autophosphorylation site of the fps/fes kinase domain. In vitro transcription/translation of a cDNA clone corresponding to the truncated c-fps/fes transcripts revealed a protein of 17 kDa. There are no translocations or rearrangements in or around the c-fps/fes gene in cell lines which express the truncated c-fps/fes transcripts. This alternative transcription of c-fps/fes may indicate a novel activation process of this proto-oncogene.
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PMID:Expression of truncated transcripts of the proto-oncogene c-fps/fes in human lymphoma and lymphoid leukemia cell lines. 137 79

The c-mos proto-oncogene is predominantly expressed in male and female germ cells and is involved in the regulation of meiosis. To investigate the mechanism of testis-specific regulation of c-mos transcription, I set out to identify the rat testis c-mos promoter. This was achieved by characterization of the rat testis c-mos transcription start site by primer extension and sequence analysis of cDNAs obtained by polymerase chain reaction amplification of 5' ends of c-mos RNA. The rat testis c-mos transcription start site is located 0.56 kb upstream of the coding region. A fragment containing the rat testis c-mos promoter directs transcription in a nuclear extract derived from rat seminiferous tubules, but not in a liver nuclear extract. DNAase I footprint analysis and gel-retardation assays showed binding of a novel testis-specific nuclear factor to the rat testis c-mos promoter at a site homologous to the testis-specific cis-acting element identified in the promoter of the RT7 gene, which is specifically expressed in haploid male germ cells.
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PMID:Identification of the testis c-mos promoter: specific activity in a seminiferous tubule-derived extract and binding of a testis-specific nuclear factor. 137 15

Human immunodeficiency virus type 2 (HIV-2) displays several features which distinguish it from HIV-1. Among the differences in these two viruses are the responses of their enhancer regions to T-cell activation. For example, stimulation of HIV-1 transcription is largely dependent on two kappa B regulatory elements. In contrast, the HIV-2 enhancer has a single kappa B site and contains additional cis-acting sequences responsive to induction. One of these sites, previously termed CD3R, is a purine-rich site, also called PuB1, which is responsive to stimulation of the CD3 component of the T-cell receptor complex and binds Elf-1, a member of the ets proto-oncogene family. In this report, we examine the interaction of the PuB1 site with other sites in the HIV-2 enhancer. We demonstrate that the PuB1 site confers responsiveness to T-cell activators only in cooperation with additional enhancer elements. Induction of the HIV-2 enhancer is dependent on at least two other cis-acting regulatory elements in addition to PuB1 and kappa B. One of these elements is another purine-rich site (PuB2), which also binds recombinant Elf-1. An adjacent region, proximal to the PuB2 ets (pets) site, shows protection in DNase footprinting experiments with extracts from Jurkat T cells. Mutation of either the kappa B, PuB1, PuB2, or pets site significantly reduces the response of the HIV-2 enhancer to T-cell stimulation, an effect which is mediated at the RNA level. Therefore, activation of the HIV-2 enhancer is dependent on at least four cis-acting elements, only one of which is found in HIV-1, which act in synergy with one another. Despite their sequence similarity, the organization and function of the HIV-2 enhancer have diverged considerably from those of HIV-1.
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PMID:Activation of the human immunodeficiency virus type 2 enhancer is dependent on purine box and kappa B regulatory elements. 150 Dec 84

P2 is the major promoter for the murine c-myc proto-oncogene. The cis-acting elements that are required for initiation of transcription from P2 have not been well defined. In this report elements involved in initiating transcription from P2 were analysed in an in vitro system. In addition to a consensus TATA element at position -28, a guanine-rich element exists at position -48. This element, termed ME1a1, increases transcription initiation when inserted into a deletion mutant that lacks it. When mutations are engineered into ME1a1 it no longer acts to increase the level of initiation. Gel-shift and DNAase I footprinting analysis indicate that Me1a1 binds a protein. ME1a1 does not show any striking similarity to other promoter elements and therefore may be a novel cis-acting element.
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PMID:Regulation of c-myc transcription in vitro: dependence on the guanine-rich promoter element ME1a1. 218 77

Members of the ras gene family encode proteins that when overproduced or mutated can transform immortalized mammalian cells. It is therefore important to understand the mechanisms by which the ras genes are regulated. The promoter region of the human Harvey ras proto-oncogene c-Ha-ras1 initiates RNA transcription at multiple sites and contains repeated copies of the hexanucleotide GGGCGG and its inverted complement CCGCCC, referred to as GC boxes. These GC boxes consist of sequences identical to those found in the SV40 early promoter, where the human cellular transcriptional factor Sp1 binds. Footprinting analysis with deoxyribonuclease I was used to show that Sp1 binds to six GC box sequences within the c-Ha-ras1 promoter. An in vivo transfection assay showed competition between the 21-base pair repeats of the SV40 promoter and the c-Ha-ras1 promoter for common regulatory factors. In this system the presence of Sp1 is apparently required for c-Ha-ras1 transcription. Analysis of deletions of the c-Ha-ras1 promoter region by means of a transient expression assay revealed that the three Sp1 binding sites closest to the RNA start sites were sufficient for full transcriptional activity.
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PMID:Binding of the Sp1 transcription factor by the human Harvey ras1 proto-oncogene promoter. 301 74

In an attempt to get an insight into the activity of mAMSA (a DNA topoisomerase II-mediated drug) on the human proto-oncogene c-myc, an in vitro system consisting of purified calf thymus DNA topoisomerase II and a c-myc DNA inserted in lambda phage was utilized. The occurrence of discrete bands, detected by hybridization of Southern blots with appropriate c-myc probes, indicated the presence of cleavage sites in the sole presence of DNA topoisomerase II. The band intensity increased in the presence of mAMSA, while no significant difference occurred in the cleavage pattern. The location of the cleavage sites along the c-myc locus revealed a striking correspondence with that of some DNase hypersensitive sites. These results indicate that DNA topoisomerase II is most certainly implicated in the mAMSA activity and that the drug stimulates the topoisomerase II cleaving activity at specific sites, which may be involved in the biological activity of the drug.
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PMID:Characterization of the topoisomerase II-induced cleavage sites in the c-myc proto-oncogene. In vitro stimulation by the antitumoral intercalating drug mAMSA. 302 49

Expression of c-myb proto-oncogene messenger RNA (mRNA) and protein has been detected principally in tumors and in normal tissue of hematopoietic origin. In each hematopoietic lineage examined, expression of the c-myb gene is markedly downregulated during hematopoietic maturation. However, the mechanism by which differential expression of the c-myb gene is regulated is not known. In murine B-lymphoid tumor cell lines, the amount of steady-state c-myb mRNA is 10 to more than 100 times greater in pre-B cell lymphomas than in B cell lymphomas and plasmacytomas. The downregulation of c-myb mRNA correlates with events at the pre-B cell-B cell junction. Differential expression of c-myb mRNA levels detected between a pre-B cell lymphoma and a mature B cell lymphoma is now shown to be mediated by a block to transcription elongation in the first intron of the c-myb locus. In addition, this developmentally regulated difference in transcriptional activity is correlated with alterations in higher order chromatin structure as reflected by changes in the patterns of hypersensitivity to deoxyribonuclease I at the 5' end of the c-myb transcription unit. Regulation of transcription elongation may provide a more sensitive mechanism for rapidly increasing and decreasing mRNA levels in response to external stimuli than regulation of the initiation of transcription.
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PMID:Differential expression of c-myb mRNA in murine B lymphomas by a block to transcription elongation. 349 14

Sequences upstream from the proto-oncogene fos were shown to be essential for its transcription. Transient expression of the chloramphenicol acetyl-transferase (CAT) gene linked to upstream sequences of the fos gene including its promoter reveals that sequences located 64 to 404 base pairs 5' to the fos cap site contain a typical transcriptional enhancer. Moreover, these enhancer sequences, which are strikingly conserved between mouse and human fos genes, coincide with a deoxyribonuclease I-hypersensitive site in the chromatin. The expression of the fos-CAT fusion genes was stimulated only two to three times by the fos inducer 12-0-tetradecanoyl phorbol-13-acetate. The fos enhancer does not appear to be tissue-specific.
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PMID:Identification of a transcriptional enhancer element upstream from the proto-oncogene fos. 386 71

The lymphocyte-specific proto-oncogene lck is transcribed from two developmentally regulated, independently functioning promoters. The proximal promoter is used in thymocytes, but not in peripheral T lymphocytes. The distal promoter operates in all stages of T cell development, but predominates in more mature cells. Both promoters lack a TATAA element and they share little sequence similarity with each other. Using transgenic mice to locate in vivo functional cis-acting regions of the murine distal promoter, we defined a region from -1786 to -2913 that is essential for consistent insertion site-independent expression of a heterologous cDNA reporter. The transgene is lymphoid specific and expressed predominantly in T cells. One of four transgenic mice bearing a shortened distal promoter (-886 to +41) expressed the reporter in the expected developmental pattern, suggesting that important regulatory elements that require favorable flanking sequences for expression are present nearer the transcription start site. The DNA sequence from -4032 to +623 contains few consensus binding sites for previously described T lymphocyte-specific trans-acting factors, and their locations do not correlate well with the functional data. However, the locations of tissue-specific modifications of chromatin structure in the promoter region, manifest as sites of DNase hypersensitivity, correlated with these two functional regions in normal mice. The identification of lck distal promoter regulatory regions provides a useful control element for deliberate expression of transgenes in mature T lymphocytes. In addition, these regulatory regions should assist in defining T cell-specific trans-acting factors.
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PMID:Functional dissection of the murine lck distal promoter. 763 95

The proto-oncogene Fgf-3 has been implicated as an important signalling molecule in vertebrate development. In the mouse, it is expressed for a limited time at a multitude of sites from embryonic day 7 to birth. Transcription of Fgf-3 initiates at three promoter regions resulting in the generation of various mRNAs which nevertheless all encode the same protein products. A 1.7kb DNA fragment which encompasses these regions was joined to the CAT reporter gene and shown to function as a promoter in embryonal carcinoma cells. In stable transfectants the promoter retains its retinoic acid inducibility, initiating transcription at the same cap-sites as the endogenous gene. In differentiated F9 cells, transient transfection of progressive and targeted deletion mutants of the promoter region has revealed at least two positive and three negative regulatory elements. With one exception, loss of these elements was shown to dramatically affect promoter activity in stable transfectants of F9 cells. However the promoter remained inducible by retinoic acid to differing degrees, apart from deletions encompassing PS-4A which essentially abolished promoter activity in both undifferentiated and differentiated cells. The sequences of these potential regulatory regions were further defined using DNase-I footprinting, revealing some similarities to consensus binding sites for known transcription factors.
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PMID:Identification of positive and negative regulatory elements involved in the retinoic acid/cAMP induction of Fgf-3 transcription in F9 cells. 826 48


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