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1
Thomson, Gabrielle Anne Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Retroelements as controlling elements in mammals." Awarded by:University of New South Wales. Biotechnology and Biomolecular Sciences, 2006. http://handle.unsw.edu.au/1959.4/26203.
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Retroelements are genomic parasites which make up ~42% of the human genome and 38% of the mouse genome. Most are degenerate, but a large number have relatively intact promoter elements, suggesting that they are capable of transcription. Transcriptionally active retroelements can perturb normal transcription units in their vicinity through a variety of mechanisms, leading to phenotypic effects and in some cases disease. This phenomenon of transcriptional interference has been observed in organisms as diverse as maize, Drosophila, and the mouse. We analysed the extent of retroelement transcription in normal and diseased tissues, by searching the mouse and human EST databases for transcripts originating in retroelement promoters, and found a large number of transcripts from LINEs, SINEs and ERVs. Retroelement transcripts were found to be initiated in both sense and antisense orientations, and to be equally as common in normal and diseased tissue. Several of these transcripts were chimeric, appearing to initiate in retroelements and reading through to cellular genes, suggestive of transcriptional interference. We have used transposon display to identify and recover retroelement transcripts in the mouse. Transcripts initiated in LINE, SINE and ERV promoters are numerous, and many are chimeric with cellular genes. Although the numbers of recovered chimeric transcripts are too large to permit rigorous analysis of more than a small proportion, some of those we have studied further appear to be authentic transcripts that may represent interference with the canonical promoters of the genes in question. Our results suggest that transcriptional interference by retroelements may be a relatively common occurrence in mammals.
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ORICCHIO, ELISA. "I retroelementi nella tumorigenesi: ruoli distinti di LINE-1 ed HERV-K nella progressione tumorale." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2008. http://hdl.handle.net/2108/399.
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I retroelementi sono sequenze altamente ripetute disperse nel genoma, che
codificano per una Trascrittasi Inversa (RT). Cellule e tessuti caratterizzati da una
elevata capacità di proliferazione e un basso grado di differenziamento (come
cellule tumorali o embrionali) esprimono alti livelli di RT che al contrario è
scarsamente espressa in tessuti terminalmente differenziati.
E’ noto da precedenti studi condotti nel nostro laboratorio che il trattamento di
diverse linee cellulari tumorali con due inibitori non nucleosidici della RT, la
nevirapina ed l’efavirenz, induce una riduzione della proliferazione e della
tumorigenicità in in vitro e d in vivo e ne promuove il differenziamento
(Mangiacasale et al., 2003; Sciamanna et al., 2005; per una review Sinibaldi-
Vallebona et al., 2006).
In questo lavoro ho dimostrato che gli inibitori della RT, inibiscono la proliferazione
solo delle cellule tumorali mentre non hanno alcun effetto significativo sulle cellule
normali. Inoltre, utilizzando la tecnica dellRNA interference (RNAi) ho identificato
due famiglie di retroelementi, LINE-1 e HERV-K, che hanno ruoli diversi nella
tumorigenesi. Infettando cellule di melanoma A375 con vettori retrovirali
adeguatamente ingegnerizzati allo scopo, ho prodotto due linee cellulari in cui
l’espressione di questi due retroelementi sia stabilmente interferita. Le cellule
interferite per il LINE-1 hanno una ridotta proliferazione, una morfologia alterata ed
un’espressione alterata di alcuni geni che regolano la proliferazione e il
differenziamento. Al contrario, le cellule A375 interferite per HERV-K non
mostrano nessun cambiamento in vitro.
A differenza di quanto osservato in vitro, entrambe le linee cellulari inoculate in
topi nudi atimici hanno una ridotta tumorigenicità rispetto alle cellule della linea
parentale.
Infine, allo scopo di sviluppare una possibile terapia genica differenziativa dei
tumori, ho sviluppato un sistema di vettori adenovirali in sostituzione di quelli retro
virali; i primi infatti offrono una serie di vantaggi rispetto ai vettori retrovirali, primo
fra tutti il fatto che queste le sequenze rimangono in forma episomale consentendo
quindi di ripetere l’infezione diverse volte allo scopo di migliorarne l’efficienza.<br>Retroelements are sequences highly repeated present in all eucaryotic genomes
and they encode for a RT that is expressed at high levels in cells and tissue types
characterized by a high proliferative potential and a low degree of differentiation
(e.g. embryonic tissues and tumor cells), whereas low RT levels are generally
found in terminally differentiated, non pathological tissue.
Previous studies have showed that inhibition of endogenous RT, using
pharmacological inhibitors, (nevirapine and efavirenz) reduces proliferation and
promotes differentiation of human tumorigenic cell lines and strongly antagonizes
tumor progression in murine models (Mangiacasaele et al., 2003 Sciamanna et al.,
2005; reviewed by Sinibaldi-Vallebona et al., 2006). In this work I have showed
that the RT inhibitors, in contrast to what observed in tumorigenic cells, does not
exert any effect on normal cells. In addition, I using a RNA interference approach
(RNAi), I assessed the different roles of two retroelements LINE-1 and HERV-K in
tumorigenesis and tumor progression. Using retroviral vectors, I produced two cell
lines, derived from A375 melanoma cells, stably interfered for the expression of
these elements. The cells in which LINE-1 expression was interfered exhibit a
reduced proliferation and significant changes in morphology, suggestive of that a
differentiation was activated. Moreover, these cells showed a reduced
tumorigenecity when injected in nude mice. Instead, cells in which HERV-K
expression was interfered the rate of proliferation and differentiation remain
unchanged compared to the parental A375 cells. However, in vivo essays their
tumorigenic potential was found to be reduced.
Finally, aiming at the development of a novel gene therapy approach for cancer
differentiation I developed an adenoviral delivery system which offers several
advantages compared to retroviruses, most important the fact that adenodelivered
sequences remain as non-integrated episomes and the infection can be
repeated several times to improve the efficiency of infection.
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Lightbourn, Gordon James. "Development of intermonoploid somatic hybrids of potato and their molecular analysis based on polymorphism for retroelement Tst1." Diss., Virginia Tech, 2004. http://hdl.handle.net/10919/28810.
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Inbred lines for hybrid crop production have been a mainstay of plant breeding. Biotechnological approaches to hasten the process are available including anther culture to halve the genome and protoplast fusion to create hybrids between incompatible partners. We applied these techniques to potato to evaluate their potential for breeding highly heterozygous, cross-pollinating species. Four families of monoploids (2n=1x=12), developed from diploid hybrids with diverse genomic constitutions but heavily favoring Solanum phureja, a primitive cultivated potato, were used in electrofusion experiments to create intermonoploid somatic hybrids (SH). The "monoploid sieve" results in the survival of only those gametes free of lethal and deleterious genes but generates sterile sporophytes, necessitating protoplast fusion for SH development. From six intermonoploid electrofusion combinations, 276 plants were regenerated over 6-9 months. Fusion conditions were optimized. Ploidy was determined by flow-cytometry and SH confirmed by microsatellite analysis. Field evaluations over three years revealed that intermonoploid SH were inferior to cultivars. Dihaploids derived by anther culture of a tetraploid intermonoploid SH were reduced in vigor with an increase in homozygosity, while 2x X 2x sexually derived populations had better yield than the SH, suggesting that producing SH introduced or eliminated factors required for productivity.
Molecular analysis of the SH was conducted to examine genomic stability through protoplast isolation and plant regeneration. Sequence specific amplified polymorphism (S-SAP) represents a hybrid system incorporating amplified fragment length polymorphism (AFLP) technology in conjunction with the use of a defined genomic sequence, e.g., retrotransposon display (RD) when the defined sequence is anchored into a consensus sequence of a retrotransposon such as the long terminal repeat (LTR) sequence of Tst1. Parental monoploids, SH and various Solanaceae were evaluated by RD. Fluorescently-labeled retrotransposon-based primers were used in the ALFexpress automated fragment analyzer system. Eleven probes from RD were created for Southern blot analysis and used to verify taxonomic relationships between selected Solanaceae. Blots of intermonoploid somatic hybrids confirmed hybridity and occasional loss of genomic fragments. No activation or replication of retrotransposons was detected. Sequencing of inter-retrotransposon amplified polymorphism (IRAP) and S-SAP fragments revealed that all fragments had the expected Tst1 retroelement and/or the AFLP adaptor sequence. BLAST analysis identified 4 of the 17 fragments sequenced as part of the chloroplast genome, a tobacco anther-specific gene, repetitive DNA, and the phytochrome F gene.<br>Ph. D.
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Meyn, Malcolm Anthony 1967. "A genetic, biochemical, and population analysis of MGL, a non-LTR retroelement from the plant pathogenic fungus Magnaporthe grisea." Diss., The University of Arizona, 1997. http://hdl.handle.net/10150/288755.
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This dissertation describes the characterization of a novel transposable element isolated from the plant pathogenic fungus Magnaporthe grisea. The sequence of MGR583, a previously reported repeated DNA fragment, was completed and shown to have features characteristic of non-LTR retroelements (LINEs). These include an element length of 5.9 kb, the lack of flanking long terminal repeats, the presence of short (6-13 bp) direct repeats flanking many element copies, and two principal open reading frames (ORFs). The first ORF is 570 amino acids in length and contains homology to the gag ORFs found in many retroelements. The second ORF is 1,295 amino acids in length and has strong homology to reverse transcriptases (RT) ORFs found in non-LTR retroelements (LINEs). In accordance with these results, the name of the repeat was changed to MGL for Magnaporthe grisea LINE. Analysis of the 3' terminus of MGL showed 90% homology to the 3' terminus of Mg-SINE, suggesting an evolutionary relationship between these two elements. A survey of the distribution of MGL in populations of M. grisea showed the element to be present in all isolates tested. Copy number was not uniform between isolates, with approximately fifty copies present in rice isolates and between less than 10 and up to 50 copies in the 17 non-rice isolates tested. A PCR-based assay was designed and used to screen M. grisea isolates for polymorphic MGL insertion loci. Thirteen polymorphic MGL insertions were scored and used to construct a phylogenetic tree that included 11 non-rice isolates and 20 rice isolates. The results strongly suggested that development of virulence on rice was a single event correlated with the acquisition of virulence on several other grass species. In addition, the observation that rearrangements occurred at one of the insertion loci in some rice isolate strains support the proposal that there is considerable plasticity in the genomes of these isolates. Finally, a yeast transposon ( Tyl) system was used to express and test the second ORF for RT activity. No activity was detected for any of the MGL RT constructs tested.
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Volkmann, Bianca [Verfasser], Thomas [Akademischer Betreuer] Gramberg, Andreas [Gutachter] Burkovski, and Andreas [Gutachter] Burkovski. "The role of TRIM proteins in retrovirus and retroelement restriction / Bianca Volkmann ; Gutachter: Andreas Burkovski, Andreas Burkovski ; Betreuer: Thomas Gramberg." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/1216332967/34.
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Adhya, Indranil. "Exhaustive Identification of the retroelement Ty1 Integrase partners in yeast Saccharomyces cerevisiae : characterization of the role of Casein kinase II in Ty1 retrotransposition in vivo." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS589.
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Les rétrotransposons LTR sont des éléments transposables très répandus chez les eucaryotes. Comme les rétrovirus, ils se répliquent par transcription inverse de leur ARN en ADNc, qui est intégré dans le génome hôte par leur propre intégrase (IN). Des études de séquençage à haut débit ont clairement établi que l'intégration ne se fait pas de façon aléatoire dans l'ensemble du génome de la cellule hôte. Des connaissances approfondies sur la biologie rétrovirale ont été acquises grâce à leur étude sur la levure utilisant le Ty1 LTR-retrotransposon comme modèle de travail. Le rétrotransposon Ty1 de la levure Saccharomyces cerevisiae intègre en amont des gènes de classe III, les gènes transcrits par l'ARN polymérase III (Pol III). Des données récentes ont révélé l'importance de l'AC40, une sous-unité de Pol III dans ce ciblage. Une interaction entre le Ty1 IN et l'AC40 est nécessaire pour le choix du site d'intégration des gènes Pol III. Néanmoins, le mécanisme moléculaire reste largement inconnu. Afin d'obtenir une vision globale de l'ensemble du phénomène qui se produit sur le site d'intégration, nous aimerions déterminer de manière exhaustive les protéines qui interagissent avec Ty1 IN et analyser leur rôle dans l'intégration de Ty1 et la transcription de l'ARN Pol III. Pour atteindre cet objectif, nous avons développé des approches protéomiques pour identifier de nouveaux partenaires cellulaires Ty1 intégraux. Nous avons identifié plusieurs nouveaux partenaires Ty1 IN qui semblent intéressants et leur rôle moléculaire dans la rétrotransposition de Ty1 sera étudié. Cependant, dans le cadre de mon doctorat, j'ai particulièrement travaillé à déchiffrer le rôle moléculaire de la protéine caséine kinase II dans la rétrotransposition de Ty1<br>LTR-retrotransposons are widespread transposable elements in eukaryotes. Like retroviruses, they replicate by reverse transcription of their RNA into cDNA, which is integrated into the host genome by their own integrase (IN). High-throughput sequencing studies clearly established that integration does not occur randomly throughout the host-cell genome. Deep insights on retroviral biology have been gained by their study in yeast using the Ty1 LTR-retrotransposon as a working model. The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae integrates upstream of class III genes, the genes transcribed by RNA polymerase III (Pol III). Recent data revealed the importance of AC40, a Pol III subunit in this targeting. An interaction between the Ty1 IN and AC40 is necessary for integration site choice at the Pol III genes. Nevertheless, the molecular mechanism remains largely unknown. To obtain a global view of the entire phenomenon that occurs on the integration site we would like to exhaustively determine the proteins that interact with Ty1 IN and analyze their role in both Ty1 integration and RNA Pol III transcription. To achieve this goal, we have developed proteomic approaches to identify new Ty1 integrase cellular partners. We have identified several novel Ty1 IN partners that seem interesting and their molecular role in Ty1 retrotransposition will be studied. However, in the tenure of my PhD, I have particularly worked to decipher the molecular role of the casein kinase II protein in Ty1 retrotransposition
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Hodes, Asher Benjamin. "Diversity-generating retroelements." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1835260431&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Nottensteiner, Mathias [Verfasser], Ralph [Akademischer Betreuer] [Gutachter] Hückelhoven, Erich J. [Gutachter] Glawischnig, and Aurélien [Gutachter] Tellier. "Molecular Characterization of Retroelement Encoded ROPIP1 as Virulence Effector of Blumeria graminis f.sp. hordei / Mathias Nottensteiner ; Gutachter: Erich J. Glawischnig, Aurélien Tellier, Ralph Hückelhoven ; Betreuer: Ralph Hückelhoven." München : Universitätsbibliothek der TU München, 2015. http://d-nb.info/112273834X/34.
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Wilson, Williamina. "Ribosomal frameshifting in retroelements." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670301.
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Mu, Sen. "Detection of Bacterial Retroelements Using Genomics." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etd/1110.
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The reverse flow of genetic information can occur when a special DNA polymerase called Reverse Transcriptase (RT) copies the genetic information in an RNA molecule back into a complementary DNA. One type of RT encoding gene found in bacteria is called a retron element. Recent bacterial genome sequencing projects have revealed many examples of retron RT genes. This gene assignment is based on comparison with a few known retron RT proteins. However, RT proteins are highly diverse in their amino acid sequences, and thus the assigned identity of these RT proteins as retrons in genome databases is questionable. One way to prove that these postulated RTs are indeed from retron elements is to see if they can produce msDNA. Retron RTs are known to synthesize a structurally unique satellite DNA called msDNA in the bacterial cells that contain them. Based on GenBank database matches to a known protein, 7 proteins designated as retron RTs were tested for their ability to synthesize msDNA. Five of these retron RTs did show evidence of producing msDNA and are from very different bacterial hosts. The other 2 RT proteins did not show any evidence that they produce msDNA.
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Arjan-Odedra, Shetal. "Regulation of exogenous retroviruses and endogenous retroelements by MOV10." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/regulation-of-exogenous-retroviruses-and-endogenous-retroelements-by-mov10(7ee91030-835b-4609-971e-f78e4e7aa0cc).html.
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Retroelements are some of the most successful parasites studied because of their ability to reverse transcribe and permanently integrate into the host genome. Host cells have, therefore, evolved multiple control mechanisms, such as cellular restriction factors, to protect their genomes from the pathogenic and mutagenic effects of retroelements. Identification of the full complement of these proteins is vital to comprehend the capacity of the host to regulate these genetic parasites. Human MOV10 is a putative RNA helicase with inhibitory or stimulatory roles in the replication of several RNA viruses, and the homologs of which play vital roles in the restriction of viruses and endogenous retroelements. Furthermore, MOV10 interacts with antiviral APOBEC3 proteins and core post-transcriptional RNA silencing machinery, all of which colocalise in cytoplasmic mRNA processing bodies and stress granules. Considering MOV10 cellular associations and homolog functions, the capacity of MOV10 to regulate the replication of a diverse panel of genetically distinct retroelements was investigated here. Ectopically overexpressed MOV10 potently restricts the replication of retroviruses as well as the propagation of LTR and non-LTR endogenous retroelements. Significantly, RNAi-mediated silencing of endogenous MOV10 enhances the replication of endogenous retroelements, but not exogenous retroviruses demonstrating that natural levels of MOV10 suppress retrotransposition. MOV10 overexpression decreases the level of HIV-1 genomic RNA packaged into nascent virions and also impacts the accumulation of reverse transcription products in target cells. The molecular mechanism/s by which MOV10 inhibits retroelements remains unclear, however, the anti-retroelement activities of MOV10 and APOBEC3 proteins are independent. Moreover, MOV10 is not essential for miRNA-mediated translation repression or slicer activity in cultured cells. In sum, ectopically overexpressed human MOV10 inhibits divergent exogenous and endogenous retroelements and, more significantly, the capacity of endogenous MOV10 to specifically suppress retrotransposition highlights it as a potential restriction factor of human retrotransposons in somatic cells.
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Vidal, Newton de Medeiros. "História evolutiva dos LTR-retrotransposons Tom, 297, 17.6 e rover em Drosophilidae." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2007. http://hdl.handle.net/10183/13628.
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Os elementos de transposição 297, 17.6 e rover de Drosophila melanogaster e Tom de D. anannassae são retrovírus endógenos de insetos filogeneticamente relacionados. Uma análise inicial da distribuição de seqüências homólogas aos retroelementos 297, 17.6 e Tom em 33 espécies Neotropicais de Drosophila, Zaprionus indianus e Scaptodrosophila latifasciaeformis, utilizando Dot Blot e PCR, indicou a distribuição restrita desses elementos ao grupo melanogaster e em Z. indianus. Essa análise inicial motivou-nos a fazer este trabalho, com o objetivo de entender a história evolutiva destes três retroelementos. Para isso, clonamos e seqüenciamos uma região da transcriptase reversa nessas espécies e buscamos nos doze genomas de Drosophila atualmente disponíveis seqüências homólogas a estes elementos. Os dados das seqüências de alguns clones indicaram a amplificação de outro elemento, o retroelemento rover, que também foi analisado neste estudo. A dinâmica evolutiva dos retroelementos Tom, 297, 17.6 e rover nos genomas de Drosophilidae são coincidentes em muitos aspectos: (1) Em uma visão geral, as filogenias de cada família são discordantes da filogenia das espécies hospedeiras; (2) Os quatro retroelementos estão envolvidos em eventos de transmissão horizontal; (3) As relações entre as seqüências dos elementos das diferentes espécies são complexas, dificultando a compreensão do cenário evolutivo dos elementos; (4) Os quatro retroelementos apresentam um menor viés na utilização de códons se comparados aos genes nucleares; (5) Pelo menos os elementos 297, 17.6 e rover apresentam valores médios de dN/dS equivalentes ao apresentado pelos genes nucleares, o que indica que essas famílias estão evoluindo sob restrição seletiva. Análises filogenéticas e de divergência nos sítios sinônimos das seqüências da transcriptase reversa dos quatro retroelementos indicam que diferentes eventos podem explicar a história evolutiva desses elementos, incluindo polimorfismo ancestral, transmissão vertical, perda estocástica e transmissão horizontal. Os dados apresentados sugerem que no mínimo 16 casos de transmissão horizontal são necessários para explicar o cenário evolutivo apresentado por esses retroelementos.<br>The transposable elements 297, 17.6 and rover from D. melanogaster and Tom from D. ananassae are closelly related insect endogenous retroviruses. An initial Dot Blot and PCR analysis of the distribution of sequences homologues to retroelements 297, 17.6 and Tom in 33 Drosophila Neotropical species, plus Zaprionus indianus and Scaptodrosophila latifasciaeformis, indicates that the distribution of these elements is restricted to the Drosophila melanogaster subgroup and Z. indianus. In order to understand the evolutionary history of these three elements, we have cloned and sequenced a transcriptase reverse region in these species and searched through sequences homologues to these elements in the twelve available Drosophila genomes. Some cloned sequences denote another element being amplified, the rover retrotransposon, which was included in this work. The evolutionary patterns of the retrotransposons Tom, 297, 17.6 and rover in Drosophilidae genomes agree in several aspects: (1) The retrotransposons phylogenies disagree with the host species phylogeny; (2) The four elements are involved in horizontal transfer events; (3) The relationships among sequences of different species are complex; (4) The four retroelements display a lower codon usage bias than nuclear genes; (5) 297, 17.6 and rover showed dN/dS ratio similar to nuclear genes dN/dS ratio, indicating selective constraints. Phylogenetic analysis and divergence in synounymous sites of reverse transcriptase sequences from these four retroelements indicate different events explaining their evolutionary history, including ancestral polymorphism, vertical transmission, stocastic loss and horizontal transfer. Our data suggest sixteen events of horizontal transfer to explain the evolutionary scenario of 297, 17.6, rover and Tom.
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Karolski, Bruno. "Efeito da inativação do retroelemento Tnt1 na regeneração de plantas de fumo." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/41/41132/tde-01112007-171834/.
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Elementos de transposição são sequências de DNA que possuem a habilidade de se transpor. Estes elementos são divididos em dois grupos de acordo com seu mecanismo de transposição. Aqueles que se transpõem diretamente a partir de moléculas de DNA são chamados de transposons e os que se transpõem através de um intermediário de RNA são chamados de retrotransposons. Os retrotransposons são encontrados nos mais diversos organismos e sua atividade é altamente regulada pelos seus hospedeiros, uma vez que no processo de transposição, efeitos deletérios decorrentes da inserção/inativação de genes podem resultar em eventos drásticos para o organismo. Foram descritos dois mecanismos de controle desses elementos. O primeiro consiste na inativação da transcrição do elemento (inibição transcricional), e o segundo consiste na degradação do mRNA pelo sistema de interferência de RNA (Inibição pós-transcricional). Apesar de serem regulados negativamente, foi verificado em plantas de fumo a indução da expressão do retrotransposon Tnt1 em situações de estresse como em injúrias e processo de regeneração. De forma geral a ativação destes é bastante intrigante e durante diversos anos estes elementos foram considerados DNA lixo ou DNA egoísta. O presente trabalho procurou avaliar a função destes elementos na regeneração de plantas de fumo através de sua inibição nessa fase. A inibição foi realizada através de construções que induzem o sistema de inteferência de RNA, clivando o mRNA dos elementos provindos de qualquer cópia no genoma. Foram selecionados indivíduos geneticamente modificados que apresentaram deficiência de desenvolvimento, ausência de raízes e resposta de hipersensibilidade.<br>Transposable elements are DNA sequences that have the ability of transposition. These elements are divided in two groups according to their transposition mechanism. Those that transpose directly as a DNA molecule are called transposons and those that are dependent on a RNA intermediate are called retrotransposons. Retrotransposons are found in various organisms and are highly regulated by their hosts. In many cases of transposition, the retroelements may be inserted into other genes, causing deleterious effects and damages to the organism. Two control mechanisms have been described in previous studies. One consists of the element transcription inactivation (transcriptional inhibition), and the second consists of the mRNA degradation by the RNA interference system (post-transcriptional inhibition). Despite the negative regulation of these elements, the induction of expression of Tnt1 retrotransposon was described in tobacco plants under stress situations such as injuries and regeneration. The function of the retroelements, in general, is not yet known although they are usually considered as junk DNA or selfish genes. Therefore, studies on the inactivation of these elements are particularly interesting. In this work, the function of these elements in tobacco plants was studied by the use of RNAi methods and analysis during the regeneration phase and plant development were evaluated. Phenotypes are described which are related to previous expression studies supporting a specific role for these elements not yet described.
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Kreimer, Ulrike [Verfasser]. "Expression und epigenetische Regulation von Retroelementen im Harnblasenkarzinom / Ulrike Kreimer." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1198477946/34.
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Khalid, Mahwish Rani, and Mahwish Rani Khalid. "Line1: Implications in the Etiology of Human Diseases, Clinical Utilities, and Pharmacological Target for Disease Treatment." Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/626716.
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Long interspersed nuclear elements-1 (Line-1 or L1) accounts for approximately 17% of the human genome. The majority of L1s are inactive, but ~100 remain retrotransposon competent (RC-L1) and retrotranspose through RNA intermediates to different locations of the genome. It is well established that L1 is involved in both disease initiation and progression via retrotransposition dependent and independent mechanisms. Retrotransposed L1 sequences disrupt loci (e.g. gene structure) in ways that lead to human disease, and activities of L1 si/piRNA, ORF1 and ORF2 proteins are implicated in the etiology and progression of human diseases such as in breast and colon cancer (Miki et al., 1992; Ohms et al., 2014). Despite these implications, very little is known about pharmacological molecules that inhibit and reverse L1’s harmful effects. The clinical utility of L1 as a player in tumorigenesis and as a biomarker for disease initiation and progression is not thoroughly understood. In this review, we analyzed the life cycle of L1, its roles in disease initiation and progression, clinical utilities and potential as a pharmacological target and a biomarker for the diagnosis and treatment of human diseases, such as cancer.
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Cilene, de Andrade Bortoleti Kyria. "Mapeamento cromossômico comparativo em espécies de Glycine Willd., Phaseolus L. e Vigna Savi." Universidade Federal de Pernambuco, 2010. https://repositorio.ufpe.br/handle/123456789/6152.
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Previous issue date: 2010<br>Um estudo genômico comparativo foi realizado mediante localização in situ de oligonucleotídeos com padrão de microssatélites [(AG)8, (AAG)5, (ACC)5, (CTC)5 e (TGA)6] e dos domínios RT dos retrotransposons Ty1-copia-like e Ty3-gypsy-like, ao longo dos cromossomos de Glycine max, Phaseolus vulgaris, P. lunatus, Vigna unguiculata e V. radiata. Os oligonucleotídeos apresentaram-se em grande proporção nos genomas analisados, porém houve variação em quantidade, organização e distribuição ao longo dos cromossomos. Na análise genômica de soja, observou-se números e tamanhos (30 a 454 pb) de sítios de repetições variáveis localizados, principalmente, em regiões de alta a moderada densidade gênica, por vezes associados a genes e elementos transponíveis. A associação da FISH e análise in silico ressaltou uma distribuição diferencial não aleatória dos oligonucleotídeos, podendo estar preferencialmente associados à heterocromatina ou à eucromatina. Os domínios RT de Ty1-copia-like e Ty3-gypsy-like foram amplificados em V. unguiculata, sendo a sequência de Ty1-copia-like menos homogênea. As análises filogenéticas enfatizaram a origem monofilética dos referidos domínios RT. A FISH evidenciou a presença de sinais dispersos e pericentroméricos, utilizando ambos retroelementos, com algumas divergências interespecíficas. Em algumas espécies, tais marcações estavam associadas a DNAr 5S e 45S, bem como localizadas em regiões heterocromáticas, enfatizando uma distribuição preferencial nos genomas estudados. Os microssatélites e retrotransposons são apontados como importantes componentes dos genomas em espécies do clado Phaseoloids (tribo Phaseoleae), propiciando uma discussão sobre o potencial estrutural e funcional dessas sequências repetitivas
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Bélanger, Kasandra. "Investigation of the Various Modes of Retroviral and Endogenous Retroelements Restriction by APOBEC3 Proteins." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34353.
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Mammals are constantly challenged by numerous pathogens that pose a threat to their health. Upon infection, retroviruses quickly integrate their genome into that of their host thereby permanently modifying it. Protein members of the APOBEC3 (A3) family exhibit cytidine deaminase activity that specifically acts on single-stranded DNA to deaminate deoxycytidine bases into deoxyuridines. This process is potentially mutagenic because uracil directs the insertion of adenine on the opposite DNA strand. High levels of mutations induced by A3 proteins in the retroviral genome ultimately inactivate progeny viruses. However, under conditions where low levels of A3 proteins are present, sub-lethal mutagenesis can occur and is generally believed to be beneficial for the virus. Powerful and affordable techniques designed to detect rare deamination events generated by these deaminases along the full length of retroviral genomes are therefore essential. Through the course of my studies, I developed such a new tool that I called HyperHRM which was instrumental to my project’s success.
In addition to the antiretroviral affects of their catalytic activity, some members of the A3 family have the ability to hinder reverse transcription independently of their enzymatic properties. Yet, the details underlying the deamination-independent restriction by the proteins remain unclear. Through my work, I have advanced our current understanding of this elusive process by defining the essential role for RNA-binding in the inhibition of the early steps of infection by APOBEC3G (A3G). I also demonstrate that the ability to bind RNA is important for the selection of DNA dinucleotides targeted for deamination by A3 enzymes. Based on the premise that the DNA context for deamination may alter viral fitness in various ways, I then investigated the gene inactivation potency of different A3 based on their preferred DNA substrate. My experiments showed that mutations introduced in a 5'CC context by A3G are much more lethal for the virus because of the high frequency of termination codons that are generated. I therefore clearly established that deamination target specificity has a strong influence on the overall restriction potency of A3 proteins and demonstrated that such specificity was linked to the ability of A3 proteins to bind RNA.
Finally, in addition to retroviruses, mobile elements such as retrotransposons can also lead to genomic instability if not properly controlled. The A3 protein family has been shown to play a crucial role in the restriction of these elements through a mechanism that is not believed to require the enzymatic activity of the proteins, although the details of the restriction mechanism are not yet understood. Here, I provide molecular insights on the potential mechanism of retrotransposon restriction by showing that the RNA-binding properties of the enzymes are not involved in the restriction of L1 retrotransposition. A complete elucidation of the modes of restriction employed by the A3 could lead to the development of a new generation of antiretroviral drugs.
Overall, my research has led to the design of a new research tool to detect and quantify A3-induced mutations in retroviruses, but more importantly, it has enabled a better understanding of how the RNA-binding abilities of A3 proteins play an essential role in the overall restriction potency of retroviruses and retrotransposons.
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Schillinger, Thomas [Verfasser], and Nora [Akademischer Betreuer] Zingler. "Diversitätsgenerierende Retroelemente – Identifikation, Klassifizierung, Phylogenie und in vitro-Funktionsanalysen / Thomas Schillinger. Betreuer: Nora Zingler." Kaiserslautern : Technische Universität Kaiserslautern, 2013. http://d-nb.info/1038694833/34.
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Heredia, Fabiana de Oliveira. "Evolução do retroelemento gypsy em espécies de Drosophila e Zaprionus indianus : uma abordagem filogenética." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2002. http://hdl.handle.net/10183/3156.
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Medhekar, Vaibhav. "Functional and immunoprotective properties of Bordetella Bsp22 & functional analysis of chromosomal diversity-generating retroelements." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1619515971&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Simão, Maryanna Cristiano. "Os elementos de transposição NLTR BS e Helena estão associados a eventos de transferência horizontal em Drosofilídeos? /." São José do Rio Preto, 2017. http://hdl.handle.net/11449/149751.
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Orientador: Claudia Marcia Aparecida Carareto<br>Banca: Gustavo Campos e Silva Kuhn<br>Banca: Luis Gustavo da Conceição Galego<br>Resumo: Este estudo teve por objetivo investigar se os retrotransposons sem LTRs (NLTRs) Helena e BS estiveram envolvidos em eventos de transferência horizontal (HT) durante a diversificação concomitante pela qual passaram as espécies do subgrupo melanogaster, do grupo melanogaster de Drosophila, e do subgênero Zaprionus, na África Tropical. O modo de transposição dos elementos NLTRs, sem a formação de um DNA intermediário, é utilizado para explicar a escassez de relatos de HT desse tipo de elemento. Estudos anteriores evidenciaram alta taxa de HT de retrotransposons com LTRs em espécies dos dois grupos citados, o que fundamentou a hipótese que essas espécies passaram por uma fase permissiva à ocorrência de HT em decorrência da sobreposição geográfica e temporal que sofreram durante sua diversificação. Para testar essa hipótese, uma região do gene da transcriptase reversa dos retrotransposons sem LTRs Helena e BS foi utilizada para investigar a ocorrência de HT entre as espécies. As sequências foram obtidas de linhagens de Zaprionus, via sequenciamento, após amplificação e clonagem, e via análises in silico nos genomas de Drosophila disponíveis nos bancos de dados, ou via sequenciamento de genomas de espécies de Drosophila e de Zaprionus. Foram realizadas análises evolutivas (análises de divergência e estimativa dos tempos de divergência entre as sequências) e filogenéticas (inferência bayesiana e verossimilhança máxima), bem como análises de network para estimar as relações de...<br>Abstract: The aim of this study was to investigate whether the retrotransposons without LTRs (NLTRs) Helena and BS were involved in horizontal transfer (HT) events during the concomitant diversification of the species of the melanogaster subgroup of the Drosophila melanogaster group, and the subgenus Zaprionus, in Tropical Africa. The mode of transposition of the NLTRs, without the formation of a DNA intermediate, is used to explain the scarcity of HT reports of this type of element. Previous studies evidenced a high HT rate of LTRs retrotransposons in species of the two groups above cited, which supported the hypothesis that these species went through a permissive phase to the occurrence of HT, as a result of the geographical and temporal overlap that they suffered during their diversification. To investigate this hypothesis, a region of the reverse transcriptase gene of the NLTR retrotransposons Helena and BS was used to investigate the occurrence of HT between the species. Sequences were obtained from Zaprionus strains, via sequencing, after amplification and cloning, and via in silico analyzes in the Drosophila genomes available in the databases, or via sequencing of Drosophila and Zaprionus genomes. Evolutionary (divergence analyses and estimation of divergence times between sequences) and phylogenetic (Bayesian inference and maximum likelihood) analyses were performed, as well as network analyses to estimate the evolutionary relationships between the sequences and, thus, to test the hypothesis of HT. The results showed that there is (i) irregular distribution of the two elements in the genera Zaprionus and Drosophila, (ii) high similarity between the sequences of the melanogaster complex and the Zaprionus subgenus, (iii) incongruities between the phylogenies of the elements and host species, and iv) times of divergence between the sequences of the two species elements of the ...<br>Mestre
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Starnes, John H. "CHARACTERIZATION AND DISTRIBUTION OF NOVEL NON-LTR RETROELEMENTS DRIVING HIGH TELOMERE RFLP DIVERSITY IN CLONAL LINES OF MAGNAPORTHE ORYZAE." UKnowledge, 2013. http://uknowledge.uky.edu/plantpath_etds/6.
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The filamentous ascomycete fungus Magnaporthe oryzae is a pathogen of over 50 genera of grasses. Two important diseases it can cause are gray leaf spot in Lolium perenne (perennial ryegrass) and blast in Oryza sativa (rice). The telomeres of M. oryzae isolates causing gray leaf spot are highly variable, and can spontaneously change during fungal culture. In this dissertation, it is shown that a rice-infecting isolate is much more stable at the telomeres than an isolate from gray leaf spot. To determine the molecular basis of telomere instability several gray leaf spot isolates telomeres were cloned, which revealed two non-LTR retrotransposons inserted into the telomere repeats. The elements have been termed Magnaporthe oryzae Telomeric Retrotransposons (MoTeRs). These elements do not have poly-A tails common to many other non-LTR retrotransposons, but instead have telomere like sequences at their 5’ end that allow them to insert into telomeres. Intact copies of MoTeRs were restricted to the telomeres of isolates causing gray leaf spot. Surveys for the presence of these elements in M. oryzae showed they were present in several host-specialized forms including gray leaf spot isolates, but were largely absent in the rice blast isolates. The absence of MoTeRs in rice blast isolates, which are relatively stable by comparison, suggested that the telomere instability in gray leaf spot isolates could be due to MoTeRs. Analyzing spontaneous alterations in telomere restriction fragment profiles of asexual progeny revealed that MoTeRs were involved. Expansion and contraction of MoTeR arrays were observed and account for some telomere restriction profile changes. New telomere formation in asexual progeny followed by MoTeR addition was also observed. Based on this evidence, MoTeRs are largely responsible for the high variability of telomere restriction profiles observed in GLS isolates.
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Jakobi, Lisa [Verfasser], and Nora [Akademischer Betreuer] Zingler. "Analyse und biochemische Charakterisierung der Protein‐Komponenten eines Diversitätsgenerierenden Retroelements aus Nostoc sp. PCC 7120 / Lisa Jakobi ; Betreuer: Nora Zingler." Kaiserslautern : Technische Universität Kaiserslautern, 2017. http://d-nb.info/1123071403/34.
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Herrmann, Alexandra [Verfasser], Thomas [Akademischer Betreuer] Gramberg, and Lars [Gutachter] Nitschke. "The role of SAMHD1 in restriction and immune sensing of retroviruses and retroelements / Alexandra Herrmann ; Gutachter: Lars Nitschke ; Betreuer: Thomas Gramberg." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2018. http://d-nb.info/1164768514/34.
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Dong, Kevin Brian. "Analysis of the role of the histone methyltransferase G9a in transcriptional repression of introduced and endogenous retroelements in murine embryonic stem cells." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/18820.
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DNA methylation and posttranslational histone modification are epigenetic marks that influence transcription of associated DNA. DNA methylation involves the direct addition of methyl groups to cytosine bases in DNA, and is associated with transcriptional repression. Histone modification can be associated with either activation or repression, and involves covalent addition of a wide variety of chemical groups to the N-terminal tails of the core histones. A relationship between DNA methylation of repetitive elements and methylation of H3 lysine 9 (H3K9) exists in Arabidopsis thaliana, where mutants in the histone methyltransferase (HMTase) KRYPTONITE (KYP) show a defect in CpNpG DNA methylation of retrotransposons. Similarly, in Neurospora crassa the H3K9 HMTase defective in methylation 5 (DIM-5) is required for DNA methylation of repetitive elements. In mice, the major H3K9 methyltransferases (MTase) in euchromatin are G9a and GLP; G9a has been shown to influence DNA methylation of a limited number of single copy genes, however, its effect on interspersed elements, such as endogenous retroviruses (ERVs) or exogenous retroviruses (XRVs) has not been characterized.
Here, I show that G9a is responsible for H3K9 dimethylation (H3K9me2) and Kap-1 recruitment at ERVs, as well as H3K9me2 and H3K9me3 at XRVs. Moreover, G9a acted upstream of DNA methylation of both XRVs and ERVs. Mutation of G9a resulted in heightened expression of XRVs, but did not influence expression of ERVs. Analysis of the mechanism behind this histone modification-DNA methylation link revealed that recruitment of the DNA methyltransferase (DNMT) De novo methyltransferase 3a (Dnmt3a) was reduced at ERVs in the absence of G9a. Surprisingly, this recruitment was partially rescued by catalytically null G9a.
Based on these observations, I conclude that G9a is targeted to ERVs and XRVs and marks these elements with H3K9me2. In addition, G9a acts upstream of DNA methylation and H3K9me3 at XRVs. The DNA methylation deficiency may be partly explained by recruitment of Dnmt3a independent of G9a’s catalytic activity. The differences observed between G9a activity at exogenous and ERVs suggest that developmental and/or evolutionary mechanisms place additional constraints on ERVs compared to XRVs.
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Pélissier, Thierry. "Analyse des regions adjacentes a l'adn satellite majeur chez arabidopsis thaliana : identification et caracterisation d'une nouvelle famille de retroelements, les elements athila." Clermont-Ferrand 2, 1995. http://www.theses.fr/1995CLF21764.
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L'heterochromatine constitutive represente un composant ubiquitaire du genome des eucaryotes superieurs dont le role biologique est encore largement meconnu. Chez de nombreux organismes et notamment chez les plantes, peu d'informations sont egalement disponibles sur la structure moleculaire precise de l'heterochromatine constitutive. Nous avons initie l'exploration de ces regions heterochromatiques chez la plante modele arabidopsis thaliana par l'analyse de regions adjacentes au satellite majeur d'arabidopsis, le satellite 180 pb qui represente certainement le principal constituant de l'heterochromatine pericentromerique chez cette espece. La selection et l'analyse de 33 clones lambda recombinants contenant potentiellement des zones de jonction entre les blocs de l'adn satellite et les regions adjacentes nous ont alors permis de montrer que les sequences immediatement adjacentes a l'adn satellite majeur chez arabidopsis sont essentiellement constituees de sequences de type moyennement repetees. La caracterisation des sequences de jonction portees par l'un de ces clones a permis la mise en evidence d'une nouvelle famille de retroelements chez arabidopsis thaliana, les elements athila. Ces elements d'environ 10. 5 kb sont presents a plus de 150 copies par genome haploide et constituent la famille d'elements transposables la plus representee dans le genome d'arabidopsis. Ils possedent plusieurs caracteristiques specifiques des retrovirus et retrotransposons comme la presence de ltrs et de sites pbs et ppt potentiels, essentiels pour la transcription inverse de ce type d'elements. Ils presentent egalement au niveau de leur domaine central deux grands orfs de 935 et 694 acides amines. Malgre certaines indications de transposition recente, l'absence d'homologie significative entre les proteines potentiellement codees par ces orfs et les proteines retrovirales, normalement impliquees dans le mecanisme de retrotranposition, suggere que la famille d'elements athila pourrait representer un des premiers exemples chez les plantes de transduction d'un gene cellulaire par un retroelement. Nos resultats indiquent egalement qu'une importante proportion des sequences moyennement repetees presentes dans les 33 phages de jonction etudies correspond a des copies defectives de l'element athila. L'analyse de la distribution genomique des elements athila a par ailleurs montre que ces elements, bien que presents a de nombreuses localisations euchromatiques, sont particulierement concentres dans ou a proximite des blocs de l'adn satellite 180 pb. Il apparait enfin que la plupart de ces elements athila heterochromatiques resultent d'evenements d'integration dans les unites de repetition de l'adn satellite 180 pb
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Pelinski, Yanís. "Chromatin Disorganization as a Regulator of Irradiation-Induced L1Md Expression and Hematopoietic Stem Cell Function Thrombopoietin Protects Hematopoietic Stem Cells from Retrotransposon-Mediated Damage by Promoting an Antiviral Response." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS122.
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L'exposition à l’irradiation, comme lors des radiothérapies, affecte l'intégrité et la fonction des cellules souches hématopoïétiques (CSH). L’IR est donc associée au développement de maladies myéloïdes liées à la thérapie, telles que les syndromes myélodysplasiques (SMD) et les leucémies myéloïdes aiguës secondaires. Par conséquent, l'étude des mécanismes moléculaires qui contribuent à la perte de fonction des CSH induite par le stress, pourrait aider à identifier les patients à risque et à trouver éventuellement de nouvelles stratégies pour prévenir ces maladies.Notre équipe a récemment découvert un nouveau mécanisme responsable de la perte de fonction des CSH murines suite à l’IR qui implique les L1Md, les sous-familles jeunes et actives des éléments LINE-1. Nous avons montré que l'expression des L1Md est augmentée suite à l'IR et que cela entraîne une accumulation de dommages à l'ADN et de défauts des CSH. Nous avons également montré que la thrombopoïétine (TPO), une cytokine de niche des CSH , prévient la perte de fonction des CSH induite par l'IR, l'accumulation de dommages à l'ADN et la dérépression des L1Md.L'analyse de microarray a montré que la TPO induit un enrichissement des gènes de signalisation de l'IFN-I dans les CSH, dont beaucoup sont des facteurs de restriction virale. Au début de ma thèse, j'ai participé à une étude qui a montré que la TPO contrôlait l'expression des L1Md par cette voie de signalisation.Les L1Md sont reconnues comme des contributeurs majeurs des réseaux de régulation des gènes. Leur expression est étroitement régulée par des mécanismes épigénétiques, tels que la marque répressive de l'histone H3K9me3.Les principaux objectifs de mon projet de thèse sont donc de :1. Comprendre les mécanismes par lesquels l’IR affecte l'épigénétique des CSH, et en particulier l'hétérochromatine.2. Déterminer si la TPO, via sa signalisation de type IFN, peut réguler la répression des L1Md par des mécanismes épigénétiques.3. Déterminer si, et comment, l'expression des L1md peut affecter l'expression génique des CSH.Des expériences de ChIP-qPCR sur des CSH un mois après IR, montrent que la dérépression des L1Md est liée à une perte de H3K9me3 au niveau de leurs promoteurs, qui est empêché par la TPO. Ces résultats ont été confirmés par des expériences de ChIPseq montrant qu'une grande majorité des loci L1Md présentaient une perte de H3K9me3 suite à l’IR par rapport à la condition non irradiée, et que cela était empêché par la TPO. Ce n'était pas le cas pour les sous-familles de rétroéléments plus anciens, comme le Lx5, ou pour les rétrovirus endogènes. Les données RNAseq ont montré que l'IR dérégule fortement le transcriptome des CSH. Une injection de TPO 1h avant l’IR empêche cela. Nous montrons également que les gènes réprimés lors de l’IR, et pas dans la condition IR+TPO, sont significativement plus susceptibles de contenir un L1Md dans leurs introns que par hasard (p<0,05). Ceci est spécifique aux L1Md et aux gènes qui sont réprimés par l’IR. Certains de ces gènes sont impliqués dans l'oncogenèse ou la fonction des CSH. L’IR induit une perte de la signature CSH. Il est intéressant de noter que 55% des gènes appartenant à la signature CSH et qui sont réprimés lors de l’IR contiennent un L1Md dans leurs introns. L'orthologue humain de 75% des gènes réprimés lors de l’IR et hébergeant une L1Md, contient également un L1 jeune chez l’homme, suggérant une fonctionne conservée dans la régulation de l'expression des gènes hématopoïétiques.Nous avons analysé plusieurs cibles et validé une diminution de l'expression en IR accompagné d'une perte de H3K9me3 au niveau de leur L1Md intronique respective.Ces résultats montrent un lien entre l'IR et l'épigénétique des CSH, et suggèrent un rôle pour les L1Md dans la régulation de l'expression des gènes hématopoïétiques<br>Exposure to ionizing radiations (IR), like in radiotherapy, affects hematopoietic stem cell (HSC) integrity and function. As a consequence, IR is associated with the development of therapy-related myeloid malignancies such as myelodysplastic syndromes (MDS) and secondary acute myeloid leukemias. Therefore, studying the molecular mechanisms that contribute towards stress-induced HSC loss of function, could help identify patients at risk and eventually find new strategies to prevent these diseases.Our team has recently uncovered a new mechanism responsible for murine HSC loss of function upon IR that involves L1Md, the young and active subfamilies of Long Interspersed Elements LINE-1. We showed that L1Md expression is increased following IR and that this leads to an accumulation of DNA damage and HSC defects. We have also shown that thrombopoietin (TPO), a niche HSC cytokine involved in self-renewal, prevents IR-induced HSC loss of function, accumulation of DNA damage and L1Md derepression.Microarray analysis had shown that TPO induced an enrichment of IFN-I signaling genes in HSCs, many of which are viral restriction factors. At the beginning of my PhD I was involved in a study that showed that TPO controlled L1Md expression via this signaling pathway. These results were published in J Exp Med in 2018, in an article in which I am co-first author.L1Md are recognized as major contributors of gene regulatory networks. Their expression is tightly regulated by epigenetic mechanisms, such as the repressive histone mark H3K9me3.The main objectives of my PhD project are thus to:1. Understand the mechanisms by which IR affects HSC epigenetics, and in particular heterochromatin.2. Determine if TPO, via its IFN-like signaling, may regulate L1Md repression through epigenetic mechanisms.3. Determine if, and how, L1md expression may impact HSC gene expression.We perfomed ChIP-qPCR experiments on HSCs one month post IR, and found that L1Md derepression is linked to a decreased H3K9me3 enrichment at their promoters, which is prevented by TPO. These results where further confirmed by ChIPseq experiments that showed that a vast majority of L1Md loci showed a reduced H3K9me3 enrichment upon IR compared to the non-irradiated condition, and that this was prevented by TPO. This was not the case for older retroelement subfamilies, such as the Lx5, or for endogenous retroviruses (ERV). RNA-seq data showed that IR strongly deregulates the HSC transcriptome. These effects are prevented by TPO injection 1h prior to IR. We also show that genes repressed upon IR, and not in the IR+TPO condition, are significantly more prone to contain an L1Md in their introns than by chance (p<0.05). This is specific for the L1Md family and for genes that are downregulated upon IR. Some of these genes are involved in oncogenesis or HSC function. IR induces a loss of the HSC signature. Interestingly, 55% of the genes belonging to the HSC signature and that are repressed upon IR contain an L1Md in their introns. The human orthologous of 75% of the genes repressed upon IR and hosting an L1Md, also host young human and primate L1, suggesting a conserved functional role of young L1 in regulating hematopoietic gene expression.We have analyzed in more details several target genes, and validated a decreased expression upon IR that is accompanied by a loss of H3K9me3 at their respective intronic L1Md.These results show for the first time a link between IR and HSC epigenetics, and suggest a role for L1Md in regulating hematopoietic gene expression
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Li, Wai-Lun Patrick. "Translation of the two proteins encoded by the mouse LINE1 retrotransposon /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Biophysics & Genetics, Human Medical Genetics Program) -- University of Colorado Denver, 2007.<br>Typescript. Includes bibliographical references (leaves 123-147). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Möller, Philipp [Verfasser], and Nora [Akademischer Betreuer] Zingler. "Identifizierung von diversitätsgenerierenden Retroelementen (DGRs) in Cyanobakterien und strukturelle Charakterisierung der Templat RNA eines DGRs aus dem Cyanobakterium Nostoc sp. PCC7120 / Philipp Möller. Betreuer: Nora Zingler." Kaiserslautern : Technische Universität Kaiserslautern, 2015. http://d-nb.info/1072621525/34.
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"Shining light on the dark matter of the genome." Tulane University, 2019.
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archives@tulane.edu<br>These studies make strides in better understanding retroelement L1 expression and regulation at the locus-specific level using a combination of sequencing technologies. A picture is painted demonstrating tissue specific patterns of L1 expression when identified stringently and confidently with our developed EL-Seq approach. As it was also determined that expressed L1s significantly correlate with regions of open chromatin, these tissue-specific patterns of L1 expression are then most likely explained by tissue-specific chromatin architecture. Evidence is also presented here that L1s in tissues respond differently with genomic stresses and perturbations as is seen in the case of aging indicating that the risk associated with L1 damage and mutagenesis is related to cell type and tissue. This is particularly notable when considering the genesis and promotion of age-related somatic diseases like epithelial cancers. L1s are commonly referred to as the dark matter of the genome, but here we illuminate its biology and regulation to better understand L1-associated damage and risk to human health.<br>0<br>Tiffany Kaul
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Vieira, Marta Alexandra Góis. "Epigenetics and the implication of env retroelements in human genome." Master's thesis, 2013. http://hdl.handle.net/10451/46034.
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Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014<br>A Epigenética é definida como as modificações que ocorrem no genoma humano, herdáveis durante a divisão celular mas que não originam uma alteração na cadeia de DNA.
Estas alterações levam à formação de um Epigenoma, que corresponde a uma representação de todos os fenómenos epigenéticos que ocorrem no genoma humano.
Este conjunto de alterações encontra-se associado com a repressão ou activação da transcrição genética e está presente nalgumas patologias, nomeadamente o cancro.
Os Retroelementos constituem uma grande porção dos elementos de transposição existentes no genoma humano e apresentam como principal característica o facto de se deslocarem para novos locais dentro do próprio genoma.
Estes estão intimamente relacionados com os eventos epigenéticos, uma vez que a metilação do DNA e a modificação das histonas está relacionada com a activação ou repressão destes elementos.<br>Epigenetics is defined as the heritable modifications occurring in the human genome during cell division, but doesn’t originate a change in the DNA chain.
These changes lead to the formation of an epigenome, which corresponds to a representation of all epigenetic phenomena occurring in the human genome.
This changes set is associated with repression or activation of gene transcription and is caracteristic of some pathologies, for example cancer.
The Retroelements constitute a large portion of the transposable elements that exists in human genome and their main characteristic is the fact that they can move to new locations within the genome itself.
These are closely related with the epigenetic events, as DNA methylation and histone modification is related to activation or repression of these elements.
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Carvalho, Margarida Morais de 1983. "Identificação, caracterização e mapeamento físico de retroelementos em Quercus suber L." Master's thesis, 2007. http://hdl.handle.net/10451/1190.
Full textAbstract:
Tese de mestrado em Biologia Celular e Biotecnologia apresentada à Universidade de Lisboa através da Faculdade de Ciências, 2007<br>LTR retrotransposons are ubiquitous mobile genetic elements in eukaryotic organisms, specially in plant kingdom, which represents their ancestrality. As retroelements, like retrovirus, they transpose through an RNA intermediate that is converted to cDNA by reverse transcriptase (RVT) and RNaseH, being then suitable for integration on the host genome. According to their genetic organization and sequence similarity they are classified as Ty1- copia or Ty3-gypsy, much like the type elements of Drosophila melanogaster. Recently it has been reported the presence of the gene env, characteristic of retrovirus and involved in their infectious capacity, in LTR retrotransposons Ty1-copia or Ty3-gypsy, which raised the hypothesis of some of these elements being in fact endogenous retroviruses. Additionaly the strong homology between retrotransposons of distant evolutionary species suggests that horizontal transmission has occurred during the evolution of these elements. In plants retrotransposons are major constituents of genomes, comprising 80% of the nuclear genome of maize. The Quercus suber species is one of the most important tree species in Portugal, both economically and ecologicaly. Nevertheless only but a few studies have been made about retrotransposons and its importance in the structure/evolution of the genome. In this work is strated the study of LTR retrotransposon in cork oak, through the identification and isolation of transcriptase reverse and env-like sequences in Ty1-copia retrotransposons. It is also studied the physical distribution of copia and gypsy-like RVT's and an env-like sequence in the genome of this species. The achieved results show the presence of copia and gypsy-like retrotransposons in cork oak, in addition to env-like sequences, spreaded through the genome and absent from heterocromatic regions, except for the gypsy-like element which exhibits a stronger signal in the rDNA 45S locus, NOR1 and in centromeres. Phylogenetic anal<br>Os retrotransposões LTR são elementos genéticos móveis ubíquos nos organismos eucariotas, em particular no reino vegetal, o que traduz a sua ancestralidade. À semelhança dos retrovirus, transpõem através de um intermediário de RNA, que é convertido em cDNA pela transcritase reversa (RVT) e RnaseH, sendo posteriormente integrado no genoma hospedeiro. Consoante a sua organização genética e homologia entre as suas sequências classificam-se em Ty1-copia ou Ty3-gypsy, à semelhança dos elementos tipo de Drosophila melanogaster. Recentemente foi descrita a presença do gene env, característico de retrovirus e envolvido na sua capacidade infecciosa, em retrotransposões LTR Ty1-copia e Ty3-gypsy, o que levantou a hipótese de alguns destes elementos serem retrovírus endógenos. Adicionalmente a elevada homologia entre retrotransposões de espécies evolutivamente distantes sugere que tenha ocorrido transmissão horizontal durante a evolução dos mesmos. Em plantas estes elementos são constituintes maioritários dos genomas, alcançando 80% do genoma nuclear de milho. A espécie Quercus suber é uma das mais importantes espécies de árvores em Portugal, a nível económico e ecológico, mas poucos estudos têm sido feitos acerca dos retroelementos e da sua importância na estrutura/evolução do genoma. Neste trabalho inicia-se o estudo dos retrotransposões LTR em sobreiro, pela identificação e isolamento de sequências de transcritases reversas (RVT's) e env-like em retrotransposões Ty1-copia. Adicionalmente estuda-se a distribuição física de RVT's copia e gypsy-like e de uma sequência env-like no genoma desta espécie. Os resultados obtidos revelam a presença de retrotransposões copia e gysy-like em sobreiro, além de sequências env-like , dispersos pelo genoma e ausentes de regiões heterocromáticas à excepção do elemento gypsy-like, que exibe uma marcação mais intensa no locus de rDNA 45S NOR1 e em centrómer