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PubMed1992

Unusual features of the retroid element PAT from the nematode Panagrellus redivivus.

The PAT retroid transposable elements differ from other retroids in that they have a 'split direct repeat' structure, i.e., and internal 300bp sequence is found repeated, about one half at each element extremity. A very abundant transcript of about 900 nt, the start of which maps to the preferentially deleted portion of PAT elements, is detected on total Panagrellus redivius RNA bearing Northern blots. A potentially corresponding ORF encodes a protein of 265 residues having a carboxy terminal Cystein motif, believed to be exclusively characteristic of the GAG protein in retoid elements. A much fainter, 1800nt long transcript, is also detected on Northern blots and maps slightly downstream of the first ORF. The predicted protein sequence of this region bears motifs typical of reverse transcriptase and RNaseH, as found in the Pol genes of retroid elements. Peptide motif similarities are greatest with the DIRS-1 element derived from Dictyostelium discoideum. The possibility of using PAT elements as transposon tagging system for Caenorhabditis elegans is discussed.

Amino Acid Sequence↗

PubMed1992

Transformation of a novel direct-repeat repressor element into a promoter and enhancer by multimerisation.

Studies on the regulation of interferon (IFN) responsive genes have mainly been centred on the highly conserved IFN stimulated responsive elements (ISREs) which can mediate type I and II IFN inducibility. To date little is known about other functional cis-acting regulatory motifs in IFN responsive genes. We report here on the identification of a repressor element in the human MxA gene defined to a 19 base pair (bp) region which houses a 9 bp direct repeat. DNA-specific protein binding on this element is not affected by IFN treatment and is distinct from ISRE binding proteins. Remarkably, contrary to expectations, when the repressor element is multimerised and spliced, in either orientation, to a reporter gene it behaves like a functional, constitutive promoter. Positioning the multimerised element in front of the SV40 enhancerless promoter also led to enhanced expression. The same protein(s) seem to bind to both the single repressor element and its multimerised form. This discovery of phenotypic reversal on a repressor element via multimerisation may have important implications in vivo.

Base Sequence↗

PubMed1993

An Alu element retroposition in two families with Huntington disease defines a new active Alu subfamily.

Alu repetitive elements represent the most common short interspersed elements (SINEs) found in primates, with an estimated 500,000 members in the haploid human genome. Considerable evidence has accumulated that these elements have dispersed in the genome by active transcription followed by retroposition, and that this process is ongoing. Sequence variation between the individual elements has lead to the hierarchical classification of Alu repeats into families and subfamilies. Young subfamilies that are still being actively transposed are of considerable interest, and the identification of one such subfamily (designated 'PV') has lead to the hypothesis that the most recent retroposition events are due to a single master Alu source gene. In the course of our search for the gene causing Huntington disease, we have detected an Alu retroposition event in two families. Sequence analysis demonstrates that this Alu element is not a member of the PV subfamily, but is similar to 5 other Alu elements in the GenBank database. Together, these Alu elements, all of which contain a 7 base-pair internal duplication, define a distinct subfamily, designated as the Sb2 subfamily, providing evidence for a second actively retroposing Alu source gene. These data provide support for multiple source genes for Alu retroposition in the human genome.

Base Sequence↗

PubMed1994

Developmentally regulated, low abundance Tec element transcripts in Euplotes crassus--implications for DNA elimination and transposition.

During macromolecular development in the ciliated protozoan, Euplotes crassus, > 105 Tec elements are precisely eliminated from the genome in a 2-4 h time interval, generating extrachromosomal circular forms of the elements. Various models have proposed a transposition-based mechanism for this excision. We have tested this hypothesis by determining the abundance of transcripts of Tec element open reading frames (ORFs) and the timing of their appearance. Transcripts are very low in abundance and are only detected by PCR amplification techniques. Thus, the low levels of transcripts argue against the participation of element-encoded functions in the Tec element elimination process. The element transcripts are only detected in RNA samples from mated cells, indicating that the micronucleus and/or developing macronucleus are transcriptionally active during the sexual phase of the life cycle. The transcription detected could allow a low level of germline-specific transposition for these elements.

Animals↗

PubMed1995

BS a novel LINE-like element in Drosophila melanogaster.

Transposable elements with long terminal inverted repeats are rare and only one family of elements of this sort has been identified in the genome of Drosophila melanogaster. An insertion associated with the HSBS mutation of the achaete-scute complex has been reported to be a second element of this type. We have determined the complete sequence of this insertion and have shown that it is in fact two copies of a new LINE-like transposable element, that we have called BS, inserted in opposite orientation 337 bp apart. Like other elements of this type, BS has two open reading frames that appear to encode a gag-like polypeptide and a reverse transcriptase. There are few complete BS elements in the five strains of D.melanogaster that we have tested and they appear to transpose infrequently. The events that may have lead to the double BS insertion are discussed in terms of the supposed mechanism of transposition of LINE-like elements.

Amino Acid Sequence↗

PubMed2006

The proteins encoded by the pogo-like Lemi1 element bind the TIRs and subterminal repeated motifs of the Arabidopsis Emigrant MITE: consequences for the transposition mechanism of MITEs.

MITEs (miniature inverted-repeated transposable elements) are a particular class of defective DNA transposons usually present within genomes as high copy number populations of highly homogeneous elements. Although an active MITE, the mPing element, has recently been characterized in rice, the transposition mechanism of MITEs remains unknown. It has been proposed that transposases of related transposons could mobilize MITEs in trans. Moreover, it has also been proposed that the presence of conserved terminal inverted-repeated (TIR) sequences could be the only requirement of MITEs for mobilization, allowing divergent or unrelated elements to be mobilized by a particular transposase. We present here evidence for a recent mobility of the Arabidopsis Emigrant MITE and we report on the capacity of the proteins encoded by the related Lemi1 transposon, a pogo-related element, to specifically bind Emigrant elements. This suggests that Lemi1 could mobilize Emigrant elements and makes the Lemi1/Emigrant couple an ideal system to study the transposition mechanism of MITEs. Our results show that Lemi1 proteins bind Emigrant TIRs but also bind cooperatively to subterminal repeated motifs. The requirement of internal sequences for the formation of proper DNA/protein structure could affect the capacity of divergent MITEs to be mobilized by distantly related transposases.

Arabidopsis↗

PubMed2002

The role of trace elements in uraemic toxicity.

Although most research on uraemic toxicity has focused on the retention or removal of organic solutes, subtle changes in the concentration of inorganic compounds are also of importance because these compounds may have significant clinical consequences. Potential clinical implications include increased risk of cancer, cardiovascular disease, immune deficiency, anaemia, renal function impairment and bone disease. In uraemic patients, the most important factor affecting trace element concentration is the degree of renal failure and modality of renal replacement therapy. Accumulation of trace elements in haemodialysis patients has resulted from dialysate contaminated with aluminium and strontium. Several trace elements have been implicated in the decline of renal function. These include arsenic, cadmium, copper, germanium, lead and mercury. In uraemic patients, aluminium, cadmium, chromium, lanthanum, strontium and zinc have been shown to accumulate in bone. In addition to substantial evidence linking aluminium to renal osteodystrophy, studies have also implicated cadmium, iron and strontium in bone disease. Studies using a rat model of chronic renal failure have demonstrated an association between lanthanum accumulation and mineralization defects characteristic of osteomalacia. Investigations of arsenic accumulation in animal models have demonstrated that speciation of trace elements potentially may alter toxicities of trace elements accumulated in uraemic patients. Conversely, the presence of uraemic toxins may also alter the uptake and toxicity of certain trace elements. Although research in uraemic patients has focused primarily on total concentrations of trace elements, the evolution of both inorganic and organic species should be considered separately.

Bone and Bones↗

PubMed1999

The age and evolution of non-LTR retrotransposable elements.

A comprehensive phylogenetic analysis was conducted of non-long-terminal-repeat (non-LTR) retrotransposons based on an extended sequence alignment of their reverse transcriptase (RT) domain. The 440 amino acid positions used included a region proposed to be similar to the "thumb" of the right-handed RT structure found in retroviruses. All identified non-LTR elements could be grouped into 11 distinct clades. Using the rates of sequence change derived from studies of the vertical inheritance of R1 and R2 elements in arthropods as a comparison, we found no evidence for the horizontal transmission of non-LTR elements. Assuming vertical descent, the phylogeny suggested that non-LTR elements are as old as eukaryotes, with each of the 11 clades dating back to the Precambrian era. The analysis enabled us to propose a simple chronology for the acquisition of different enzymatic domains in the evolution of the non-LTR class of retrotransposons. The first non-LTR elements were sequence specific by virtue of a restriction-enzyme-like endonuclease located downstream of the RT domain. Evolving from this original group were elements (eight clades) that acquired an apurinic-apyrimidic endonuclease-like domain upstream of the RT domain. Finally, four of these clades have inherited an RNase H domain downstream of the RT domain. The phylogenies of the AP endonuclease and RNase H domains were also determined for this report and are consistent with the monophyletic acquisition of these domains. These studies represent the most comprehensive effort to date to trace the evolution of a major class of transposable elements.

Amino Acid Sequence↗

PubMed1999

Evolution of sea urchin retroviral-like (SURL) elements: evidence from 40 echinoid species.

We conducted a phylogenetic survey of sea urchin retroviral-like (SURL) retrotransposable elements in 33 species of the class Echinoidea (sea urchins, sand dollars, and heart urchins). A 263-bp fragment from the coding region of the reverse transcriptase (RT) gene was amplified, cloned, and sequenced. Phylogenetic relationships of the elements isolated from independent clones, along with those from seven additional echinoid species obtained earlier by Springer et al., were compared with host phylogeny. Vertical transmission and the presence of paralogous sequences that diverged prior to host speciation can explain most of the phylogenetic relationships among SURL elements. Rates of evolution were estimated from cases in which SURL and host phylogenies were concordant. In agreement with conclusions reached previously by Springer et al., average rates of synonymous substitution were comparable with those of single-copy sea urchin DNA. High ratios of synonymous to nonsynonymous substitution suggest that the RT of the elements is under strong purifying selection. However, a high proportion (approximately 15%) of elements with deleterious frameshifts and stop codons and an increase of the ratio of synonymous to nonsynonymous substitutions with divergence time show that in the short term this selection is relaxed. Despite the predominance of vertical transmission, sequence similarity of 83%-94% for SURL elements from hosts that have been separated for 200 Myr suggests four cases of apparent horizontal transfer between the ancestors of the extant echinoid species. In three additional cases, elements with identical RT sequences were found in sea urchin species separated for a minimum of 3 Myr. Thus, horizontal transfer plays a role in the evolution of this retrotransposon family.

Animals↗

PubMed2000

Molecular and evolutionary analysis of two divergent subfamilies of a novel miniature inverted repeat transposable element in the yellow fever mosquito, Aedes aegypti.

A novel family of miniature inverted repeat transposable elements (MITEs) named Pony was discovered in the yellow fever mosquito, Aedes aegypti. It has all the characteristics of MITEs, including terminal inverted repeats, no coding potential, A+T richness, small size, and the potential to form stable secondary structures. Past mobility of PONY: was indicated by the identification of two Pony insertions which resulted in the duplication of the TA dinucleotide targets. Two highly divergent subfamilies, A and B, were identified in A. aegypti based on sequence comparison and phylogenetic analysis of 38 elements. These subfamilies showed less than 62% sequence similarity. However, within each subfamily, most elements were highly conserved, and multiple subgroups could be identified, indicating recent amplifications from different source genes. Different scenarios are presented to explain the evolutionary history of these subfamilies. Both subfamilies share conserved terminal inverted repeats similar to those of the Tc2 DNA transposons in Caenorhabditis elegans, indicating that Pony may have been borrowing the transposition machinery from a Tc2-like transposon in mosquitoes. In addition to the terminal inverted repeats, full-length and partial subterminal repeats of a sequence motif TTGATTCAWATTCCGRACA represent the majority of the conservation between the two subfamilies, indicating that they may be important structural and/or functional components of the Pony elements. In contrast to known autonomous DNA transposons, both subfamilies of PONY: are highly reiterated in the A. aegypti genome (8,400 and 9, 900 copies, respectively). Together, they constitute approximately 1. 1% of the entire genome. Pony elements were frequently found near other transposable elements or in the noncoding regions of genes. The relative abundance of MITEs varies in eukaryotic genomes, which may have in part contributed to the different organizations of the genomes and reflect different types of interactions between the hosts and these widespread transposable elements.

Aedes↗

PubMed2004

Dietary intakes of seven elements of importance in radiological protection by asian population: comparison with ICRP data.

Within the framework of a Coordinated Research Project (CRP) organized by the International Atomic Energy Agency, Vienna, the daily dietary intakes of seven elements by adult populations living in nine Asian countries were estimated. The countries that participated in the study were Bangladesh, China, India, Indonesia, Japan, Pakistan, Philippines, South Korea (Republic of Korea, ROK), and Vietnam and together they represented more than half of the world population. The seven elements studied were calcium, cesium, iodine, potassium, strontium, thorium, and uranium. These elements have chemical and biological similarity to some of the radionuclides abundantly encountered during nuclear power production and therefore data on these elements could provide important information on their biokinetic behavior. Analyses of diet samples for these seven elements were carried out using highly sensitive and reliable analytical techniques. One thousand one hundred and sixty analytical determinations were made on two hundred and twenty samples of typical diets consumed in these countries to estimate the daily intakes of these elements by the adult Asian population. The median daily dietary intakes for the adult Asian population were found to be 0.45 g calcium, 7 microg cesium, 90 microg iodine, 1.75 g potassium, 1.65 mg strontium, 1 microg thorium, and 1 microg uranium. When compared with the intakes proposed for ICRP Reference Man by International Commission for Radiological Protection, these intakes were lower by factors of 0.41 for calcium, 0.7 for cesium, 0.45 for iodine, 0.53 for potassium, 0.87 for strontium, 0.33 for thorium, and 0.52 for uranium. The lower daily intakes of calcium, cesium, and iodine by Asian population could be due to significantly lower consumption of milk and milk products, which are rich in these elements. The significantly lower intake of calcium in most of the Asian countries may lead to higher uptake of fission nuclide 90Sr and could result in perhaps higher internal radiation dose. The use of highly sensitive and reliable analytical methods resulted in accurate and lower intake values obtained for thorium and uranium, which suggest that radiation dose from their ingestion at natural background levels is likely to be lower than what may be concluded from ICRP data.

Asia↗

PubMed2006

Nelfinavir induces liposarcoma apoptosis and cell cycle arrest by upregulating sterol regulatory element binding protein-1.

"HIV protease-induced lipodystrophy syndrome" is associated with the use of HIV protease inhibitors for treatment of HIV infection. In-vitro studies suggest that alteration of sterol regulatory element binding protein-1 levels underlie its pathogenesis. We postulated that HIV protease inhibitors may represent a novel class of antiliposarcoma agents. SW872, FU-DDLS-1 and LiSa-2 liposarcoma, and HT1080 and 293 nonliposarcoma cell lines were treated with HIV protease inhibitors (nelfinavir, ritonavir, saquinavir, indinavir and amprenavir), and clonogenic assays were performed. Nelfinavir exhibited the most potent inhibition of clonogenicity, and further assays for proliferation, cell cycle and apoptosis were performed with nelfinavir. Immunoblots were performed for sterol regulatory element binding protein-1, proapoptotic and cell cycle-related protein expression after nelfinavir treatment. Finally, a sterol regulatory element binding protein-1-inducible SW872 cell line was developed to examine the phenotype resulting from upregulated sterol regulatory element binding protein-1. Nelfinavir selectively inhibited clonogenicity and proliferation, and induced G1 cell cycle block and induced apoptosis in a dose-dependent manner in SW872 and LiSa-2 cells, whereas it had minimal or no effect on these parameters in FU-DDLS-1 or nonliposarcoma cells. Nelfinavir induced significant sterol regulatory element binding protein-1 expression in a dose-dependent and time-dependent fashion in sensitive SW872 and LiSa-2 cells, modestly in HT1080 cells, but not in nelfinavir-insensitive FU-DDLS-1 and 293 cells without inducing adipocytic differentiation. Forced expression of sterol regulatory element binding protein-1 in inducible-SW872 cells led to the induction of proapoptotic and antiproliferative proteins, and consequent reduction of cellular proliferation. Our data indicate that nelfinavir represents a novel class of antiliposarcoma agent that acts by selectively upregulating sterol regulatory element binding protein-1 expression in liposarcomas.

Antineoplastic Agents↗

PubMed1979

Trace elements in the atmosphere.

The distribution and behaviour of particulate trace elements in the atmosphere have been studied by continuous measurements for 5 years at seven non-urban sites in the United Kingdom. Samples have been taken regularly of airborne dust, rainwater and dry deposition: these have been analysed for up to 36 elements. Concentrations of trace elements vary considerably between sites but the relative concentrations are among uniform: this suggests similarity of origin or good atmospheric mixing. By comparing the relative concentrations with those in soil it is possible to differentiate between trace elements that are derived from soil and those that may be attributed to industrial activity. This classification is supported by estimates of the particle sizes in air. The deposition of trace elements can be related to the concentrations presnet in soil and to the annual removal by crops. Retrospective analyses of stored samples from one site describe the history of trace element concentrations in air since 1957. The sea surface is considered as a possible source of atmospheric trace elements.

Aerosols↗

PubMed1981

Levels, distribution and chemical forms of trace elements in food plants.

The content of trace elements in plants can vary widely, depending upon the composition of the soil in which they grow, other environmental factors, and the species or cultivar of the plant. A high growth rate of the plant may cause internal 'dilution' of trace elements. Complex formation with soil organic colloids and compounds, cell wall material and ligands in and inside the cell membranes are of critical importance in uptake, though most evidence shows that it is the free metal ion in the external solution that is absorbed; the detailed mechanisms are still unknown. Other processes such as excretion of organic compounds, reductants and hydrogen ions from the root greatly alter availability of trace metals, and iron has to be reduced to the ferrous form before uptake. The mean composition of plant shoots is affected by age and season; element mobility in the xylem and phloem determines translocation, and hence concentrations in individual parts of the plant. The rate of retranslocation can be strongly affected by the abundance of the element. Symptoms of deficiency or excess are well documented, but are often not dependable. The essentiality of the trace metals depends upon their function as part of enzymes, and these are briefly reviewed, with stress on processes in plants. Only a small fraction of the total amount of an element is bound in the enzyme; of the remainder, some is present as the free metal ion (Mn) or as complexes of small molecular mass (Cu, Zn, Ni, Fe), the rest being bound to cell wall material. Certain species or genotypes have resistance against high levels of some elements in the soil. Several mechanisms may be involved, one being very strong binding to root cell walls. There are also large genetic differences in susceptibility to trace element deficiencies.

Age Factors↗

PubMed1990

A wide variety of DNA sequences can functionally replace a yeast TATA element for transcriptional activation.

We created a library of DNA molecules in which the required TATA element of a yeast gal-his3 promoter is replaced by random-sequence oligomers averaging 16 bp in length. Surprisingly, 1% of such random sequences functionally replace the native yeast TATA element. In many cases, sequences completely unrelated to the consensus TATA element (TATAAA) stimulate transcription with equal or increased efficiency. Transcription mediated by these synthetic elements requires GAL4 and is initiated from normal his3 initiation sites, suggesting that it occurs by a mechanism indistinguishable from that involving wild-type TATA elements. Many, but not all, of these elements act as substrates for yeast TFIID in reconstituted transcription reactions in vitro. These observations indicate that yeast TFIID can stimulate transcription from TATA elements whose sequences differ from the consensus, and they suggest the possibility of alternative factors that may provide a related function for transcriptional activation.

Animals↗

PubMed2003

CACTA transposons in Triticeae. A diverse family of high-copy repetitive elements.

In comparison with retrotransposons, which comprise the majority of the Triticeae genomes, very few class 2 transposons have been described in these genomes. Based on the recent discovery of a local accumulation of CACTA elements at the Glu-A3 loci in the two wheat species Triticum monococcum and Triticum durum, we performed a database search for additional such elements in Triticeae spp. A combination of BLAST search and dot-plot analysis of publicly available Triticeae sequences led to the identification of 41 CACTA elements. Only seven of them encode a protein similar to known transposases, whereas the other 34 are considered to be deletion derivatives. A detailed characterization of the identified elements allowed a further classification into seven subgroups. The major subgroup, designated the "Caspar " family, was shown by hybridization to be present in at least 3,000 copies in the T. monococcum genome. The close association of numerous CACTA elements with genes and the identification of several similar elements in sorghum (Sorghum bicolor) and rice (Oryza sativa) led to the conclusion that CACTA elements contribute significantly to genome size and to organization and evolution of grass genomes.

DNA Transposable Elements↗

PubMed2003

A novel WRKY transcription factor, SUSIBA2, participates in sugar signaling in barley by binding to the sugar-responsive elements of the iso1 promoter.

SURE (sugar responsive) is a cis element in plant sugar signaling. The SURE element was reported first for potato, in which it confers sugar responsiveness to the patatin promoter. A SURE binding transcription factor has not been isolated. We have isolated a transcription factor cDNA from barley and purified the corresponding protein. The transcription factor, SUSIBA2 (sugar signaling in barley), belongs to the WRKY proteins and was shown to bind to SURE and W-box elements but not to the SP8a element in the iso1 promoter. Nuclear localization of SUSIBA2 was demonstrated in a transient assay system with a SUSIBA2:green fluorescent protein fusion protein. Exploiting the novel transcription factor oligodeoxynucleotide decoy strategy with transformed barley endosperm provided experimental evidence for the importance of the SURE elements in iso1 transcription. Antibodies against SUSIBA2 were produced, and the expression pattern for susiba2 was determined at the RNA and protein levels. It was found that susiba2 is expressed in endosperm but not in leaves. Transcription of susiba2 is sugar inducible, and ectopic susiba2 expression was obtained in sugar-treated leaves. Likewise, binding to SURE elements was observed for nuclear extracts from sugar-treated but not from control barley leaves. The temporal expression of susiba2 in barley endosperm followed that of iso1 and endogenous sucrose levels, with a peak at approximately 12 days after pollination. Our data indicate that SUSIBA2 binds to the SURE elements in the barley iso1 promoter as an activator. Furthermore, they show that SUSIBA2 is a regulatory transcription factor in starch synthesis and demonstrate the involvement of a WRKY protein in carbohydrate anabolism. Orthologs to SUSIBA2 were isolated from rice and wheat endosperm.

Amino Acid Sequence↗

PubMed1990

A DNA-binding protein factor recognizes two binding domains within the octopine synthase enhancer element.

A protein that binds to the enhancing element of the octopine synthase gene has been identified in nuclear extracts from maize cell suspension cultures. Two protein-DNA complexes are distinguishable by electrophoretic mobility in gel retardation assays. Footprint analyses of these low and high molecular weight complexes show, respectively, half and complete protection of the ocs-element DNA from cleavage by methidiumpropyl-EDTA.FE(II). Two lines of evidence indicate that the element has two recognition sites, each of which can bind identical protein units. Elements that are mutated in one or the other half and form only the low molecular weight complex interfere with the formation of both the low and high molecular weight complexes by the wild-type element. Protein isolated from a complex with only one binding site occupied can bind to the wild-type ocs-element and generate complexes with protein occupying one or both binding sites. Occupation of both sites of the ocs-element is a prerequisite for transcriptional enhancement.

Amino Acid Oxidoreductases↗