The Experts below are selected from a list of 40620 Experts worldwide ranked by ideXlab platform
Peter A. Peterson - One of the best experts on this subject based on the ideXlab platform.
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Historical Overview of Transposable Element Research
Methods in molecular biology (Clifton N.J.), 2013Co-Authors: Peter A. PetersonAbstract:Research on Transposable Elements began nearly 100 years ago with classical genetic experiments. Remarkably, many of the activities of Transposable Elements, such as the ability to transpose, to induce chromosome rearrangements, to undergo cycles of activity and inactivity, and to affect expression of neighboring genes, were described by geneticists long before transposons were molecularly isolated. This chapter traces the historical roots of Transposable Element research, describing the scientists, their observations, and interpretations as they sought to understand the enigma of Transposable Elements.
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The Ac and Uq Transposable Element systems in maize: interactions among components.
Genetics, 1992Co-Authors: E. E. O. Caldwell, Peter A. PetersonAbstract:Components of the Uq and Ac Transposable Element systems interact. A large sample of Ds-containing and ruq-containing alleles were tested against Uq and Ac. The Uq Elements elicit a mutable response from only one of the classes of Ds Elements (Ds1) in the Ac family. This response is similar to the response from ruq to Uq. In contrast, Ac elicits mutable responses from all Ds and ruq Elements tested. This represents a lack of reciprocity of interaction for the components of the two Elements, Ac and Uq. Further, two atypical Ac and Uq Elements (Ac2 and Uq-Mn) were examined. All ruq and Ds Elements tested respond to four doses of Ac2. (Responses to lower doses were not compared.) Only the ruq (Ds1) containing alleles respond to Uq-Mn. The other Ds containing alleles were nonresponsive. The finding of nonreciprocating interaction between components suggests a heterogeneous nature for Transposable Element systems in maize.
Daniel L. Hartl - One of the best experts on this subject based on the ideXlab platform.
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Germline transformation of Drosophila virilis with the Transposable Element mariner.
Genetics, 1996Co-Authors: Allan R. Lohe, Daniel L. HartlAbstract:An important goal in molecular genetics has been to identify a Transposable Element that might serve as an efficient transformation vector in diverse species of insects. The Transposable Element mariner occurs naturally in a wide variety of insects. Although virtually all mariner Elements are nonfunctional, the Mosl Element isolated from Drosophila mauritiana is functional. Mosl was injected into the pole-cell region of embryos of D. virilis , which last shared a common ancestor with D. mauritiana 40 million years ago. Mosl PCR fragments were detected in several pools of DNA from progeny of injected animals, and backcross lines were established. Because G o lines were pooled, possibly only one transformation event was actually obtained, yielding a minimum frequency of 4%. Mosl segregated in a Mendelian fashion, demonstrating chromosomal integration. The copy number increased by spontaneous mobilization. In situ hybridization confirmed multiple polymorphic locations of Mosl. Integration results in a characteristic 2-bp TA duplication. One Mosl Element integrated into a tandem array of 370-bp repeats. Some copies may have integrated into heterochromatin, as evidenced by their ability to support PCR amplification despite absence of a signal in Southern and in situ hybridizations.
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The Transposable Element mariner mediates germline transformation in Drosophila melanogaster.
Genetics, 1993Co-Authors: D A Lidholm, Allan R. Lohe, Daniel L. HartlAbstract:A vector for germline transformation in Drosophila melanogaster was constructed using the Transposable Element mariner. The vector, denoted pMlwB, contains a mariner Element disrupted by an insertion containing the wild-type white gene from D. melanogaster, the beta-galactosidase gene from Escherichia coli and sequences that enable plasmid replication and selection in E. coli. The white gene is controlled by the promoter of the D. melanogaster gene for heat-shock protein 70, and the beta-galactosidase gene is flanked upstream by the promoter of the Transposable Element P as well as that of mariner. The MlwB Element was introduced into the germline of D. melanogaster by co-injection into embryos with an active mariner Element, Mos1, which codes for a functional transposase and serves as a helper. Two independent germline insertions were isolated and characterized. The results show that the MlwB Element inserted into the genome in a mariner-dependent manner with the termini of the inverted repeats inserted at a TA dinucleotide. Both insertions exhibit an unexpected degree of germline and somatic stability, even in the presence of an active mariner Element in the genetic background. These results demonstrate that the mariner Transposable Element, which is small (1286 bp) and relatively homogeneous in size among different copies, is nevertheless capable of promoting the insertion of the large (13.2 kb) MlwB Element. Because of the widespread phylogenetic distribution of mariner among insects, these results suggest that mariner might provide a wide host-range transformation vector for insects.
Keith A. Crandall - One of the best experts on this subject based on the ideXlab platform.
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Telescope: Characterization of the retrotranscriptome by accurate estimation of Transposable Element expression.
PLoS computational biology, 2019Co-Authors: Matthew L. Bendall, Miguel De Mulder, Luis P. Iñiguez, Aarón Lecanda-sánchez, Marcos Pérez-losada, Mario A. Ostrowski, R. Brad Jones, Lubbertus C. F. Mulder, Gustavo Reyes-terán, Keith A. CrandallAbstract:Characterization of Human Endogenous Retrovirus (HERV) expression within the transcriptomic landscape using RNA-seq is complicated by uncertainty in fragment assignment because of sequence similarity. We present Telescope, a computational software tool that provides accurate estimation of Transposable Element expression (retrotranscriptome) resolved to specific genomic locations. Telescope directly addresses uncertainty in fragment assignment by reassigning ambiguously mapped fragments to the most probable source transcript as determined within a Bayesian statistical model. We demonstrate the utility of our approach through single locus analysis of HERV expression in 13 ENCODE cell types. When examined at this resolution, we find that the magnitude and breadth of the retrotranscriptome can be vastly different among cell types. Furthermore, our approach is robust to differences in sequencing technology and demonstrates that the retrotranscriptome has potential to be used for cell type identification. We compared our tool with other approaches for quantifying Transposable Element (TE) expression, and found that Telescope has the greatest resolution, as it estimates expression at specific TE insertions rather than at the TE subfamily level. Telescope performs highly accurate quantification of the retrotranscriptomic landscape in RNA-seq experiments, revealing a differential complexity in the Transposable Element biology of complex systems not previously observed. Telescope is available at https://github.com/mlbendall/telescope.
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Telescope: Characterization of the retrotranscriptome by accurate estimation of Transposable Element expression
2018Co-Authors: Matthew L. Bendall, Miguel De Mulder, Luis P. Iñiguez, Aarón Lecanda-sánchez, Marcos Pérez-losada, Mario A. Ostrowski, R. Brad Jones, Lubbertus C. F. Mulder, Gustavo Reyes-terán, Keith A. CrandallAbstract:Characterization of Human Endogenous Retrovirus (HERV) expression within the transcriptomic landscape using RNA-seq is complicated by uncertainty in fragment assignment because of sequence similarity. We present Telescope, a computational software tool that provides accurate estimation of Transposable Element expression (retrotranscriptome) resolved to specific genomic locations. Telescope directly addresses uncertainty in fragment assignment by reassigning ambiguously mapped fragments to the most probable source transcript as determined within a Bayesian statistical model. We demonstrate the utility of our approach through single locus analysis of HERV expression in 13 ENCODE cell types. When examined at this resolution, we find that the magnitude and breadth of the retrotranscriptome can be vastly different among cell types. Furthermore, our approach is robust to differences in sequencing technology, and demonstrates that the retrotranscriptome has potential to be used for cell type identification. Telescope performs highly accurate quantification of the retrotranscriptomic landscape in RNA-seq experiments, revealing a differential complexity in the Transposable Element biology of complex systems not previously observed. Telescope is available at github.com/mlbendall/telescope.
Bess Frost - One of the best experts on this subject based on the ideXlab platform.
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JUMP AROUND, JUMP AROUND: Transposable Element ACTIVATION IN NEURODEGENERATIVE TAUOPATHY
Innovation in Aging, 2019Co-Authors: Bess Frost, Wenyan Sun, Hanie Samimi, Habil ZareAbstract:Abstract Transposable Elements, or “jumping genes,” constitute ~45% of the human genome. We have identified Transposable Element activation as a key mediator of neurodegeneration in tauopathies, a group of disorders that are pathologically defined by deposits of tau protein in the brain. Cellular defenses that limit Transposable Element mobilization include 1) formation of silencing heterochromatin and 2) generation of piwi-interacting RNAs (piRNAs) that clear Transposable Element transcripts. Using genetic approaches in Drosophila models of tauopathy, we find evidence for a causal relationship between tau-induced heterochromatin decondensation and piRNA depletion, Transposable Element mobilization, and neurodegeneration. 3TC, an FDA-approved inhibitor of reverse transcriptase, suppresses Transposable Element mobilization and neuronal death in tau transgenic Drosophila. We detect a significant increase in transcripts of the human endogenous retrovirus class of Transposable Elements in postmortem human Alzheimer’s disease brains. Our data identify Transposable Element activation as a conserved, pharmacologically targetable driver of neurodegeneration in tauopathy.
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Pathogenic tau-induced piRNA depletion promotes neuronal death through Transposable Element dysregulation in neurodegenerative tauopathies
Nature neuroscience, 2018Co-Authors: Wenyan Sun, Hanie Samimi, Habil Zare, Maria Gamez, Bess FrostAbstract:Transposable Elements, known colloquially as ‘jumping genes’, constitute approximately 45% of the human genome. Cells utilize epigenetic defenses to limit Transposable Element jumping, including formation of silencing heterochromatin and generation of piwi-interacting RNAs (piRNAs), small RNAs that facilitate clearance of Transposable Element transcripts. Here we utilize Drosophila melanogaster and postmortem human brain samples to identify Transposable Element dysregulation as a key mediator of neuronal death in tauopathies, a group of neurodegenerative disorders that are pathologically characterized by deposits of tau protein in the brain. Mechanistically, we find that heterochromatin decondensation and reduction of piwi and piRNAs drive Transposable Element dysregulation in tauopathy. We further report a significant increase in transcripts of the endogenous retrovirus class of Transposable Elements in human Alzheimer’s disease and progressive supranuclear palsy, suggesting that Transposable Element dysregulation is conserved in human tauopathy. Taken together, our data identify heterochromatin decondensation, piwi and piRNA depletion and consequent Transposable Element dysregulation as a pharmacologically targetable, mechanistic driver of neurodegeneration in tauopathy. Transposable Elements, or ‘jumping genes’, constitute ~45% of the human genome. Sun et. al. report that jumping gene dysregulation is a pharmacologically targetable driver of cell death in neurodegenerative tauopathies, including Alzheimer’s disease.
Allan R. Lohe - One of the best experts on this subject based on the ideXlab platform.
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Germline transformation of Drosophila virilis with the Transposable Element mariner.
Genetics, 1996Co-Authors: Allan R. Lohe, Daniel L. HartlAbstract:An important goal in molecular genetics has been to identify a Transposable Element that might serve as an efficient transformation vector in diverse species of insects. The Transposable Element mariner occurs naturally in a wide variety of insects. Although virtually all mariner Elements are nonfunctional, the Mosl Element isolated from Drosophila mauritiana is functional. Mosl was injected into the pole-cell region of embryos of D. virilis , which last shared a common ancestor with D. mauritiana 40 million years ago. Mosl PCR fragments were detected in several pools of DNA from progeny of injected animals, and backcross lines were established. Because G o lines were pooled, possibly only one transformation event was actually obtained, yielding a minimum frequency of 4%. Mosl segregated in a Mendelian fashion, demonstrating chromosomal integration. The copy number increased by spontaneous mobilization. In situ hybridization confirmed multiple polymorphic locations of Mosl. Integration results in a characteristic 2-bp TA duplication. One Mosl Element integrated into a tandem array of 370-bp repeats. Some copies may have integrated into heterochromatin, as evidenced by their ability to support PCR amplification despite absence of a signal in Southern and in situ hybridizations.
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The Transposable Element mariner mediates germline transformation in Drosophila melanogaster.
Genetics, 1993Co-Authors: D A Lidholm, Allan R. Lohe, Daniel L. HartlAbstract:A vector for germline transformation in Drosophila melanogaster was constructed using the Transposable Element mariner. The vector, denoted pMlwB, contains a mariner Element disrupted by an insertion containing the wild-type white gene from D. melanogaster, the beta-galactosidase gene from Escherichia coli and sequences that enable plasmid replication and selection in E. coli. The white gene is controlled by the promoter of the D. melanogaster gene for heat-shock protein 70, and the beta-galactosidase gene is flanked upstream by the promoter of the Transposable Element P as well as that of mariner. The MlwB Element was introduced into the germline of D. melanogaster by co-injection into embryos with an active mariner Element, Mos1, which codes for a functional transposase and serves as a helper. Two independent germline insertions were isolated and characterized. The results show that the MlwB Element inserted into the genome in a mariner-dependent manner with the termini of the inverted repeats inserted at a TA dinucleotide. Both insertions exhibit an unexpected degree of germline and somatic stability, even in the presence of an active mariner Element in the genetic background. These results demonstrate that the mariner Transposable Element, which is small (1286 bp) and relatively homogeneous in size among different copies, is nevertheless capable of promoting the insertion of the large (13.2 kb) MlwB Element. Because of the widespread phylogenetic distribution of mariner among insects, these results suggest that mariner might provide a wide host-range transformation vector for insects.
