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At least 307 records · Page 17Linked to original sources
PubMed1999

Transcription of the human thyrotropin-releasing hormone receptor gene-analysis of basal promoter elements and glucocorticoid response elements.

The gene for the human thyrotropin-releasing hormone receptor (TRHR) spans 35 kb and contains three exons and two introns (Matre et al. (1999) J. Neurochem. 72, 1-11). Despite a reported transcription start site (TSS) mapped to position -885 upstream of the translation initiation codon (Iwasaki et al. (1996) J. Biol. Chem. 271, 22183-8), we found cell type specific promoter activity directed by a fragment downstream of this site (-770 to +1). To elucidate the basis for this unexpected activity, we analyzed basal promoter elements in this region of the gene. One divergent TATA box, TTTAAA in position -759, was found by mutational analysis to be critical for promoter activity, providing a likely explanation for the basal activity observed. This proximal region apparently contains several promoter elements, including Pit-1 binding sequences within the first intron of the TRHR gene as previously reported. Here we describe the analysis of two putative glucocorticoid response elements (GREs) that we identified in this region, one (distal) half site overlapping the proposed TSS at -885 and one (proximal) full site within the first intron at position -624. Accordingly, stimulation of rat pituitary GH3 and GH4C1 cells with dexamethasone strongly enhanced transcription activity of a reporter construct containing the distal GRE half site and the proximal GRE site. Both sites bound the glucocorticoid receptor (GR) in a specific manner. Deletion of the distal GRE half site abolished the dexamethasone induction of CAT transcription, as did mutations in the proximal site. We therefore conclude that both sites are necessary for regulation of the TRHR gene transcription by glucocorticoids.

Animals↗
PubMed1989

The bz-rcy allele of the Cy transposable element system of Zea mays contains a Mu-like element insertion.

The receptive component of the Cy transposable element system (rcy:Mu7) at the Bz locus of Zea mays L. is 2.2 kb and has long terminal inverted repeats. The insertion is flanked by a 9 bp duplication. In the presence of an autonomous Cy element in the genome, rcy:Mu7 is excised from bz-rcy in a manner consistent with a model suggested previously. The termini of rcy:Mu7 have 85% sequence similarity with the Mu1 element of Z. mays. This is consistent with the observation that Mu1 can behave genetically like a receptive component of the Cy system.

Alleles↗
PubMed2002

Association of different mobile elements to generate novel integrative elements.

Among the more important problems in modern hospitals is the prevalence of bacterial pathogens expressing resistance to multiple antimicrobial agents. The frequency of multiresistance suggests mechanisms by which bacterial species can concentrate and efficiently exchange a variety of resistance determinants. Mechanisms by which this occurs include insertion of transposons within transposons, coalescence through the activity of insertion sequences and the employment of integrons. In some instances, more than one of these mechanisms is involved in creating large multiresistance genetic elements. The association of the elements with transferable elements or transposons may promote rapid dissemination among clinical strains, and create further opportunities for inclusion of additional resistance determinants.

Bacteria↗
PubMed1990

Trace element reference values in tissues from inhabitants of the European community. I. A study of 46 elements in urine, blood and serum of Italian subjects.

Neutron activation analysis-electrothermal atomic absorption spectroscopy (ETA-AAS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) have been used for the determination of 46 elements in urine, 35 in blood and 26 in serum of unexposed Italian subjects living in the same region (Lombardy). The results allowed the proposal of reference values for various elements determined in more than 350 healthy subjects, these being Ag, Al, As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Se, Tl, V, Zn, in urine; Ag, As, Bi, Cd, Cr, Co, Cu, Hg, Pb, Se, Tl, Zn in blood; and Ag, Al, Be, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, Zn in serum (or plasma). For all other elements indicative values are suggested. In addition to the mean value and the "reference range", a "range of uncertainty" and an upper limit above which metabolic abnormalities could be expected have also been defined on the basis of simple statistical considerations.

Humans↗
PubMed1992

Trace element reference values in tissues from inhabitants of the European Community. II. Examples of strategy adopted and trace element analysis of blood, lymph nodes and cerebrospinal fluid of Italian subjects.

The EURO TERVIHT (Trace Element Reference Values in Human Tissues), recently initiated, aims to establish and compare trace metal reference values in inhabitants from the different EC countries. The project anticipates international cooperation of specialized chemical and toxicological laboratories in Western Europe. In order to overcome the well known and intolerable high fluctuation in published trace metal concentrations in body fluids and tissues, which are mostly due to poor analysis, this paper gives recommendations and strategies for approaching 'background' values measurement practised in the EURO TERVIHT. The focus of the paper is more on quality rather than on quantity of data with particular aspects: (i) well-described protocol for the selection/composition of reference groups (extended epidemiological data plus clinical status); (ii) numerous pre-analytical factors, among which are of paramount importance are ultraclean laboratory air, container material, storage conditions at -20 degrees C; (iii) statistical treatment of the data and the expression of the analytical results (use of refined statistical analysis such as the Lilliefors test to define the type of distribution, normal or log-normal). Results reported here concern the determination of trace elements in whole blood of more than 350 Italian subjects which allowed the proposal of 'reference values' for 12 elements. In lymph nodes and cerebrospinal (CSF) the degree of information acquired is only sufficient to suggest 'indicative' of 'informative' values.

Computers↗
PubMed1994

Element reference values in tissues from inhabitants of the European Community. VI. Review of elements in blood, plasma and urine and a critical evaluation of reference values for the United Kingdom population.

Reference values for the concentration of elements in whole blood for the UK population are presented together with estimates for concentrations in plasma and urine. The blood data, when compared with other values obtained for Belgium, Denmark and Italy, obtained through the EURO-Terviht programme of the European Union, together with data from other countries, indicate similar concentrations. The data provide a basis for identifying the expected levels for the non-occupational exposed population against which differences attributable to various states of well-being, morbidity and mortality can be evaluated. However, it is also apparent that significant differences do exist which are related to geography and diet. In order to consider these differences, further improvements in the determination of elements in human tissues and fluids are required. Particular attention should be paid to that proportion of an element in the environment which is bioavailable together with its toxicity.

Autopsy↗
PubMed1998

Trace element reference values in tissues from inhabitants of the European Union. X. A study of 13 elements in blood and urine of a United Kingdom population.

Electrothermal atomic absorption spectrophotometry (ETAAS), inductively coupled plasma mass spectrometry (ICP-MS) and neutron activation analysis (NAA) were used for the quantitative determination of 13 trace elements in urine and seven trace elements in whole blood of healthy unexposed British subjects living in three regions of the United Kingdom. Careful control of pre-analytical and analytical factors have enabled the results obtained from more than 200 individuals to be used in proposing reference intervals for the following elements; Al, As, Cd, Co, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Se, Tl in urine, and Cd, Cr, Hg, Mn, Pb, Se and Tl in blood.

Adolescent↗
PubMed2001

cis-acting DNA regulatory elements, including the retinoic acid response element, are required for tissue specific laminin B1 promoter/lacZ expression in transgenic mice.

The LAMB1 gene encodes the laminin beta1 subunit of laminin, an extracellular matrix protein. Using several transgenic mouse lines containing various lengths of the LAMB1 promoter driving lacZ reporter gene expression, regions of LAMB1 promoter that contain cis-acting DNA regulatory element(s) have been identified. The 3.9LAMB1betagal transgene is expressed in various tissues during development. LAMB1 transgene expression is observed in a selective set of nephrons of the neonatal and adult kidneys. The cis-acting DNA regulatory elements responsible for LAMB1 transgene expression in ovaries and in juvenile kidneys are present between -'1.4 and -0.7 kb relative to the transcription start site, while those of adult kidneys are located between -2.5 and -1.4 kb. The LAMB1 transgene is also expressed in the epididymis of 1 week old transgenic mice. Mutation of the retinoic acid response element (RARE) in the context of the 3.9LAMB1betagal transgene results in loss of LAMB1 transgene expression in all tissues. Thus, sequences between -2.5 and -0.7 kb plus the RARE are required for appropriate expression of the LAMB1 transgene in mice.

Animals↗
PubMed2002

An element in the 3' untranslated region of human LINE-1 retrotransposon mRNA binds NXF1(TAP) and can function as a nuclear export element.

Export of unspliced mRNA to the cytoplasm is required for the replication of all retroviruses. In simian type D retroviruses, the RNA export is mediated by the constitutive transport element (CTE) that binds the cellular nuclear export factor 1, NXF1(TAP). To search for potential cellular RNA substrates for NXF1, we have set up an in vitro selection procedure, using an RNA library expressed from total human genomic DNA. A sequence that was isolated most frequently as independent clones exhibits extensive homology to the 3' untranslated region of expressed LINE1 (L1) retrotransposons. This region, termed L1-NXF1 binding element (L1-NBE) bears no structural resemblance to the viral CTE, but binds NXF1 as strongly as CTE, based on gel mobility shift competition assays. A deletion analysis of the NXF1 protein reveals that CTE and L1-NBE have different, but overlapping, binding domains on NXF1. Placed in an intron, L1-NBE is capable of mediating nuclear export of lariat RNA species in Xenopus laevis oocytes and of an unspliced HIV-1 derived RNA in human 293 cells, suggesting that it may function as a nuclear export element for the intronless L1 mRNA.

3' Untranslated Regions↗
PubMed2006

A family of conserved noncoding elements derived from an ancient transposable element.

The evolutionary origin of the conserved noncoding elements (CNEs) in the human genome remains poorly understood but may hold important clues to their biological functions. Here, we report the discovery of a CNE family with approximately 124 instances in the human genome that demonstrates a clear signature of having been derived from an ancient transposon. The CNE family is also present in the chicken genome, although typically not at orthologous locations. The CNE family is closely related to the active transposon SINE3 in zebrafish and also to a previously uncharacterized transposon in the coelacanth, the so-called "living fossil" belonging to the lobe-finned fish lineage. The mammal, bird, zebrafish, and coelacanth families all share a highly similar core element of approximately 180 bp but have important differences in their 5' and 3' ends. The core element has thus been preserved over 450 million years of evolution, implying an important biological function. In addition, we identify 95 additional CNE families that likely predate the mammalian radiation. The results highlight both the creative role of transposons and the importance of CNE families.

Animals↗
PubMed1999

The Caenorhabditis elegans homologue of thioredoxin reductase contains a selenocysteine insertion sequence (SECIS) element that differs from mammalian SECIS elements but directs selenocysteine incorporation.

Thioredoxin reductases (TRR) serve critical roles in maintaining cellular redox states. Two isoforms of TRR have been identified in mammals: both contain a penultimate selenocysteine residue that is essential for catalytic activity. A search of the genome of the invertebrate, Caenorhabditis elegans, reveals a gene highly homologous to mammalian TRR, with a TGA selenocysteine codon at the corresponding position. A selenocysteyl-tRNA was identified in this organism several years ago, but no selenoproteins have been identified experimentally. Herein we report the first identification of a C. elegans selenoprotein. By (75)Se labeling of C. elegans, one major band was identified, which migrated with the predicted mobility of the C. elegans TRR homologue. Western analysis with an antibody against human TRR provides strong evidence for identification of the C. elegans selenoprotein as a member of the TRR family. The 3'-untranslated region of this gene contains a selenocysteine insertion sequence (SECIS) element that deviates at one position from the previously invariant consensus "AUGA." Nonetheless, this element functions to direct selenocysteine incorporation in mammalian cells, suggesting conservation of the factors recognizing SECIS elements from worm to man.

Amino Acid Sequence↗
PubMed1999

The activation of the rat copper/zinc superoxide dismutase gene by hydrogen peroxide through the hydrogen peroxide-responsive element and by paraquat and heat shock through the same heat shock element.

Copper/zinc superoxide dismutase (SOD1) protects cells against oxidative hazards by the dismutation of superoxide radicals. The promoter activity of the SOD1 gene was increased 3-5-fold by hydrogen peroxide, paraquat (PQ) and heat shock. Functional analyses of the regulatory region of the SOD1 gene by deletions, mutations, and heterologous promoter systems confirmed the induction of the SOD1 gene by H(2)O(2) through the hydrogen peroxide-responsive element (HRE) (between nucleotides -533 and -520). Gel mobility shift assays showed that the existence of an H(2)O(2)-inducible protein bound to the oligonucleotide of the HRE. Similar analyses showed that the heat shock activated the SOD1 promoter through the heat shock element (HSE) (between nucleotides -185 and -171). A strong specific far-shifted complex with the oligonucleotide of the HSE was observed by the treatment of heat shock. When cells were treated with PQ, a strong far-shifted complex with the HSE was observed and was competed out by the cold HSE probe, indicating that PQ also activated the SOD1 promoter through the same HSE site. It is very interesting to note that chemical and physical stresses, such as PQ and heat shock, respectively, activated the SOD1 promoter through the same cis-element HSE. These results indicate that the SOD1 was inducible by H(2)O(2) through the HRE and by PQ and heat shock through the same HSE to protect cells from oxidative hazards.

Animals↗
PubMed2006

Identification of nerve growth factor-responsive element of the TCL1 promoter as a novel negative regulatory element.

The serine/threonine kinase, Akt (protein kinase B) plays a central role in the regulation of intracellular cell survival. Recently, we demonstrated that the proto-oncogene TCL1, overexpressed in human T-cell prolymphocytic leukemia, is an Akt kinase co-activator. Tightly restricted TCL1 gene expression in early developmental cells suggested that the TCL1 gene is regulated at a transcriptional level. To characterize how TCL1 gene expression is regulated, we cloned the 5'-promoter of the TCL1 gene located at human chromosome 14q32. The 5'-TCL1 promoter region contains a TATA box with cis-regulatory elements for Nur77/NGFI-B (nerve growth factor-responsive element (NBRE), CCAAGGTCA), NFkappaB, and fork head transcription factor. Nur77/NGFI-B, an orphan receptor superfamily transcription factor implicated in T-cell apoptosis, is a substrate for Akt. We hypothesized that TCL1 transactivity is regulated through Akt-induced phosphorylation of Nur77/NGFI-B in vivo. In an electrophoretic mobility shift assay with chromosomal immunoprecipitation assays, wild-type Nur77, but not S350A mutant Nur77, could specifically bind to TCL1-NBRE. A luciferase assay demonstrated that TCL1-NBRE is required for inhibition of TCL1 transactivity upon nerve growth factor/platelet-derived growth factor stimulation, which activates Akt and phosphorylates Nur77. Using a chromosomal immunoprecipitation assay with reverse transcription-PCR, nerve growth factor stimulation inhibited binding of endogenous Nur77 to TCL1-NBRE, in turn, suppressing TCL1 gene expression. The results together establish that TCL1-NBRE is a novel negative regulatory element of Nur77 (NGFI-B). To the best of our knowledge, TCL1-NBRE is the first direct target of Nur77 involving the regulation of intracellular cell death survival. This Akt-induced inhibitory mechanism of TCL1 should play an important role in immunological and/or neuronal development in vivo.

Animals↗
PubMed2000

The skin barrier: analysis of physiologically important elements and trace elements.

Changes in the properties of the skin barrier should have correlates in the physiological status of the differentiating epidermal cells. However, the quantitative distributions of physiologically important elements and trace elements of the skin has been a neglected area of research for lack of tools to investigate this highly differentiated tissue. With the event of the particle probes, the electron microprobe and the scanning proton microprobe, it has become possible to investigate different aspects of normal skin physiology as well as pathophysiological processes. In addition penetration profiles of allergenic metals can be demonstrated with the trace element sensitive proton probe. Future approaches to the study of skin physiology in normal and pathological conditions should incorporate other techniques including immunological and biochemical tagging of particular cells to achieve a broad basis for interpretations of data.

Allergens↗
PubMed1975

Elemental analysis of honey as an indicator of pollution. Forty-seven elements in honeys produced near highway, industrial, and mining areas.

Nineteen samples of honey taken from grocery shelves, near zinc mines, adjacent to an industrial area, and near a major highway, and one sample collected in 1899 were subjected to spark source mass spectrometry to determine the concentration of most of 47 elements in the honey. Certain samples of honey produced by bees in the vicinity of the New York State Thruway appeared to contain elevated levels of certain elements known to be emitted by traffic, such as aluminum, barium, calcuim, copper, magnesium, nickel, palladium, and silicon, but the true source of these elements was uncertain. Honey that had come into contact with metal containers in processing contained the greatest amounts of zinc and tin.

Air Pollution↗
PubMed2004

Transposition of the Tol2 element, an Ac-like element from the Japanese medaka fish Oryzias latipes, in mouse embryonic stem cells.

The Tol2 transposable element of the Japanese medaka fish belongs to the hAT family of transposons including hobo of Drosophila, Ac of maize, and Tam3 of snapdragon. To date, Tol2 is the only natural transposon in vertebrates that has ever been shown to encode a fully functional transposase. It has not been known, however, whether Tol2 can transpose in vertebrates other than fish. We report here transposition of Tol2 in mouse embryonic stem (ES) cells. We constructed a transposon donor plasmid containing a nonautonomous Tol2 element with the neomycin resistance gene and a helper plasmid capable of expressing the transposase and introduced the donor plasmid with various amounts of the helper plasmid by electroporation into mouse ES cells. The number of G418-resistant ES colonies increased as the amount of helper plasmid was increased, in a dose-dependent manner, indicating that the transposase activity elevated the integration efficiency. These G418-resistant ES colonies were cloned and the structure of the junction of the integrated Tol2 element and the genomic DNA was analyzed by inverse PCR. In those clones, Tol2 was surrounded by mouse genomic sequences and an 8-bp direct repeat was created adjacent to both ends of Tol2, indicating that Tol2 was integrated in the genome through transposition. The Tol2 transposon system is thus active in mouse as well as in fish. We propose that it should be used as a genetic tool to develop novel gene transfer, transgenesis, and mutagenesis methods in mammals.

Animals↗
PubMed2001

Insertion preference of maize and rice miniature inverted repeat transposable elements as revealed by the analysis of nested elements.

A 128-bp insertion into the maize waxy-B2 allele led to the discovery of Tourist, a family of miniature inverted repeat transposable elements (MITEs). As a special category of nonautonomous elements, MITEs are distinguished by their high copy number, small size, and close association with plant genes. In maize, some Tourist elements (named Tourist-Zm) are present as adjacent or nested insertions. To determine whether the formation of multimers is a common feature of MITEs, we performed a more thorough survey, including an estimation of the proportion of multimers, with 30.2 Mb of publicly available rice genome sequence. Among the 6600 MITEs identified, >10% were present as multimers. The proportion of multimers differs for different MITE families. For some MITE families, a high frequency of self-insertions was found. The fact that all 340 multimers are unique indicates that the multimers are not capable of further amplification.

Base Sequence↗
PubMed1996

Differential binding of cAMP-responsive-element (CRE)-binding protein-1 and activating transcription factor-2 to a CRE-like element in the human tissue-type plasminogen activator (t-PA) gene promoter correlates with opposite regulation of t-PA by phorbol ester in HT-1080 and HeLa cells.

The human tissue-type plasminogen activator gene (t-PA) is induced by the phorbol ester, phorbol 12-myristate 13-acetate (PMA), in HeLa cells. Previous studies in transfected HeLa cells identified two cis-acting regulatory elements within the t-PA gene promoter responsible for both constitutive and PMA-inducible expression. One element differs from the consensus cAMP response element (CRE) by a single nucleotide substitution (referred to in this report as t-PACRE) and another which bears similarity to the AP-2 recognition sequence. In HT-1080 fibrosarcoma cells, t-PA mRNA levels are expressed at higher constitutive levels and are suppressed by PMA. Nuclear run-on transcription experiments indicate that PMA-mediated suppression of t-PA in these cells is associated with a decrease in t-PA gene template activity. We designed experiments to determine whether nuclear t-PACRE or AP-2-like binding proteins were differentially expressed in HeLa and HT-1080 cells and, accordingly, if these could be correlated with the opposite effect of PMA on t-PA expression. Band shift analyses indicated that the migration profiles of HeLa and HT-1080 nuclear proteins interacting with the AP-2-like site were indistinguishable; however, those produced with the t-PACRE binding site were qualitatively and quantitatively distinct. The distribution of t-PACRE binding proteins in these cells was investigated in a supershift assay using specific antibodies against members of the fos/jun and CRE-binding protein (CREB)/activating transcription factor (ATF) families. In HT-1080 cells, CREB-1 was the most prominent t-PACRE-binding activity detected and was greatly increased in cells treated with PMA. In contrast, CREB-1 activity was absent in HeLa cells, but antibodies specific for ATF-2 produced a marked supershifted complex which was unaffected by PMA treatment. Since CREB-1 can repress transcription of other target genes (including c-jun) via association with identical cis-acting CRE-like sequences, we suggest that the mechanism for the transcriptional down-regulation of t-PA by PMA in HT-1080 cells requires CREB-1 binding to the t-PACRE while ATF-2, by associating with the same site, plays a role in PMA-mediated induction of t-PA in HeLa cells.

Activating Transcription Factor 2↗