30 results on '"Cristofari, Gael"'
Search Results
2. A genome-wide screen reveals new regulators of the 2-cell-like cell state
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Gupta, Nikhil, Yakhou, Lounis, Albert, Julien Richard, Azogui, Anaelle, Ferry, Laure, Kirsh, Olivier, Miura, Fumihito, Battault, Sarah, Yamaguchi, Kosuke, Laisné, Marthe, Domrane, Cécilia, Bonhomme, Frédéric, Sarkar, Arpita, Delagrange, Marine, Ducos, Bertrand, Cristofari, Gael, Ito, Takashi, Greenberg, Maxim V. C., and Defossez, Pierre-Antoine
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- 2023
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3. Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites
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Lanciano, Sophie, Philippe, Claude, Sarkar, Arpita, Pratella, David, Domrane, Cécilia, Doucet, Aurélien J., van Essen, Dominic, Saccani, Simona, Ferry, Laure, Defossez, Pierre-Antoine, and Cristofari, Gael
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- 2024
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4. TASOR epigenetic repressor cooperates with a CNOT1 RNA degradation pathway to repress HIV
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Matkovic, Roy, Morel, Marina, Lanciano, Sophie, Larrous, Pauline, Martin, Benjamin, Bejjani, Fabienne, Vauthier, Virginie, Hansen, Maike M. K., Emiliani, Stéphane, Cristofari, Gael, Gallois-Montbrun, Sarah, and Margottin-Goguet, Florence
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- 2022
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5. Nascent RNA m6A modification at the heart of the gene–retrotransposon conflict
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Billon, Victor and Cristofari, Gael
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- 2021
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6. A genetic screen identifies BEND3 as a regulator of bivalent gene expression and global DNA methylation
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Yakhou, Lounis, primary, Azogui, Anaelle, additional, Gupta, Nikhil, additional, Richard Albert, Julien, additional, Miura, Fumihito, additional, Ferry, Laure, additional, Yamaguchi, Kosuke, additional, Battault, Sarah, additional, Therizols, Pierre, additional, Bonhomme, Frédéric, additional, Bethuel, Elouan, additional, Sarkar, Arpita, additional, Greenberg, Maxim V C, additional, Arimondo, Paola B, additional, Cristofari, Gael, additional, Kirsh, Olivier, additional, Ito, Takashi, additional, and Defossez, Pierre-Antoine, additional
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- 2023
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7. Cancer Immunotherapy: How to Exploit Transposable Elements?
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Lanciano, Sophie, primary and Cristofari, Gael, additional
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- 2023
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8. The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition
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Tristán-Ramos, Pablo, Rubio-Roldan, Alejandro, Peris, Guillermo, Sánchez, Laura, Amador-Cubero, Suyapa, Viollet, Sebastien, Cristofari, Gael, and Heras, Sara R.
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- 2020
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9. Flip-flop genomics: Charting inversions in the human population
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Lanciano, Sophie, primary and Cristofari, Gael, additional
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- 2022
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10. Snapshots of genetic copy-and-paste machinery in action
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Cristofari, Gael
- Abstract
LINE-1 DNA elements self-duplicate, inserting the copy into new regions of the genome — a key process in chromosome evolution. Structures of the machinery that performs this process in humans are now reported.
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- 2024
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11. Reevaluation of Telomerase Inhibition by Quadruplex Ligands and Their Mechanisms of Action
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De Cian, Anne, Cristofari, Gael, Reichenbach, Patrick, De Lemos, Elsa, Monchaud, David, Teulade-Fichou, Marie-Paule, Shin-ya, Kazuo, Lacroix, Laurent, Lingner, Joachim, and Mergny, Jean-Louis
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- 2007
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12. Locus-specific chromatin profiling of evolutionarily young transposable elements
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Taylor, Darren, primary, Lowe, Robert, additional, Philippe, Claude, additional, Cheng, Kevin C L, additional, Grant, Olivia A, additional, Zabet, Nicolae Radu, additional, Cristofari, Gael, additional, and Branco, Miguel R, additional
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- 2021
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13. The catalytic and the RNA subunits of human telomerase are required to immortalize equid primary fibroblasts
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Vidale, Pamela, Magnani, Elisa, Nergadze, Solomon G., Santagostino, Marco, Cristofari, Gael, Smirnova, Alexandra, Mondello, Chiara, and Giulotto, Elena
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- 2012
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14. The OncoAge Consortium: Linking Aging and Oncology from Bench to Bedside and Back Again
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Hofman, Paul, Ayache, Nicholas, Barbry, Pascal, Barlaud, Michel, Bel, Audrey, Blancou, Philippe, Checler, Frédéric, Chevillard, Sylvie, Cristofari, Gael, Demory, Mathilde, Esnault, Vincent, Falandry, Claire, Gilson, Eric, Guerin, Olivier, Glaichenhaus, Nicolas, Guigay, Joël, Ilie, Marius, Mari, Bernard, Marquette, Charles-Hugo, Paquis-Flucklinger, Véronique, Prate, Frédéric, Saintigny, Pierre, Seitz-Polsky, Barbara, Skhiri, Taycir, van Obberghen-Schilling, Ellen, Obberghen, Emmanuel, Yvan-Charvet, Laurent, Laboratoire de Pathologie Clinique et Expérimentale. Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia-Antipolis (I3S) / Projet MEDIACODING, Signal, Images et Systèmes (Laboratoire I3S - SIS), Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Laboratoire d'Informatique, Signaux, et Systèmes de Sophia Antipolis (I3S), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre d’Innovation et d’Usages en Santé (CIUS), Laboratoire de Cancérologie Expérimentale (LCE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Département de Néphrologie - Hôpital Pasteur [Nice], Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Cimiez, pôle Gériatrie Gérontologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Institut de Biologie Valrose (IBV), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de PhysioMédecine Moléculaire (LP2M), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice, Ligue Departementale des Alpes Maritimes de Lutte contre le Cancer, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
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education ,research ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,well-being ,Perspective ,aging ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,optimization ,elderly ,[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation - Abstract
International audience; It is generally accepted that carcinogenesis and aging are two biological processes, which are known to be associated. Notably, the frequency of certain cancers (including lung cancer), increases significantly with the age of patients and there is now a wealth of data showing that multiple mechanisms leading to malignant transformation and to aging are interconnected, defining the so-called common biology of aging and cancer. OncoAge, a consortium launched in 2015, brings together the multidisciplinary expertise of leading public hospital services and academic laboratories to foster the transfer of scientific knowledge rapidly acquired in the fields of cancer biology and aging into innovative medical practice and silver economy development. This is achieved through the development of shared technical platforms (for research on genome stability, (epi)genetics, biobanking, immunology, metabolism, and artificial intelligence), clinical research projects, clinical trials, and education. OncoAge focuses mainly on two pilot pathologies, which benefit from the expertise of several members, namely lung and head and neck cancers. This review outlines the broad strategic directions and key advances of OncoAge and summarizes some of the issues faced by this consortium, as well as the short-and long-term perspectives.
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- 2019
15. The oncoage consortium: linking aging and oncology from bench to bedside and back again
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Ayache, Nicholas, Barbry, Pascal, Barlaud, Michel, Bel, Audrey, Blancou, Philippe, Checler, Frederic, Chevillard, Sylvie, Cristofari, Gael, Demory, Mathilde, Esnault, Vincent, Falandry, Claire, Gilson, Eric, Guerin, Olivier, Glaichenhaus, Nicolas, Guigay, Joel, Ilie, Marius, Mari, Bernard, Marquette, Charles-Hugo, Paquis-Flucklinger, Veronique, Prate, Frederic, Saintigny, Pierre, Seitz-Polsky, Barbara, Skhiri, Taycir, Van Obberghen-Schilling, Ellen, Van Obberghen, Emmanuel, Yvan-Charvet, Laurent, and Hofman, Paul
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aging ,cancer ,optimization ,research ,education ,elderly ,well-being ,Cancer - Abstract
It is generally accepted that carcinogenesis and aging are two biological processes, which are known to be associated. Notably, the frequency of certain cancers (including lung cancer), increases significantly with the age of patients and there is now a wealth of data showing that multiple mechanisms leading to malignant transformation and to aging are interconnected, defining the so-called common biology of aging and cancer. OncoAge, a consortium launched in 2015, brings together the multidisciplinary expertise of leading public hospital services and academic laboratories to foster the transfer of scientific knowledge rapidly acquired in the fields of cancer biology and aging into innovative medical practice and silver economy development. This is achieved through the development of shared technical platforms (for research on genome stability, (epi)genetics, biobanking, immunology, metabolism, and artificial intelligence), clinical research projects, clinical trials, and education. OncoAge focuses mainly on two pilot pathologies, which benefit from the expertise of several members, namely lung and head and neck cancers. This review outlines the broad strategic directions and key advances of OncoAge and summarizes some of the issues faced by this consortium, as well as the short- and long-term perspectives.
- Published
- 2019
16. The Landscape of L1 Retrotransposons in the Human Genome Is Shaped by Pre-insertion Sequence Biases and Post-insertion Selection
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Sultana, Tania, primary, van Essen, Dominic, additional, Siol, Oliver, additional, Bailly-Bechet, Marc, additional, Philippe, Claude, additional, Zine El Aabidine, Amal, additional, Pioger, Léo, additional, Nigumann, Pilvi, additional, Saccani, Simona, additional, Andrau, Jean-Christophe, additional, Gilbert, Nicolas, additional, and Cristofari, Gael, additional
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- 2019
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17. Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts
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Albrengues, Jean, Bertero, Thomas, Grasset, Eloise, Bonan, Stephanie, Maiel, Majdi, Bourget, Isabelle, Philippe, Claude, Herraiz Serrano, Cecilia, Benamar, Samia, Croce, Olivier, Sanz-Moreno, Victoria, Meneguzzi, Guerrino, Feral, Chloe C., Cristofari, Gael, and Gaggioli, Cedric
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embryonic structures - Abstract
Carcinoma-associated fibroblasts (CAF) mediate the onset of a proinvasive tumour microenvironment. The proinflammatory cytokine LIF reprograms fibroblasts into a proinvasive phenotype, which promotes extracellular matrix remodelling and collective invasion of cancer cells. Here we unveil that exposure to LIF initiates an epigenetic switch leading to the constitutive activation of JAK1/STAT3 signalling, which results in sustained proinvasive activity of CAF. Mechanistically, p300-histone acetyltransferase acetylates STAT3, which, in turn, upregulates and activates the DNMT3b DNA methyltransferase. DNMT3b methylates CpG sites of the SHP-1 phosphatase promoter, which abrogates SHP-1 expression, and results in constitutive phosphorylation of JAK1. Sustained JAK1/STAT3 signalling is maintained by DNA methyltransferase DNMT1. Consistently, in human lung and head and neck carcinomas, STAT3 acetylation and phosphorylation are inversely correlated with SHP-1 expression. Combined inhibition of DNMT activities and JAK signalling, in vitro and in vivo, results in long-term reversion of CAF-associated proinvasive activity and restoration of the wild-type fibroblast phenotype.
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- 2015
18. Fingering the ends: how to make new telomeres
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Cristofari, Gael and Linger, Joachim
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Telomeres -- Research ,Developmental biology -- Research ,Reverse transcriptase -- Physiological aspects ,Biological sciences - Published
- 2003
19. International Congress on Transposable elements (ICTE 2016) in Saint Malo: mobile elements under the sun of Brittany
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Lesage, Pascale, primary, Bétermier, Mireille, additional, Bridier-Nahmias, Antoine, additional, Chandler, Michael, additional, Chambeyron, Séverine, additional, Cristofari, Gael, additional, Gilbert, Nicolas, additional, Quesneville, Hadi, additional, Vaury, Chantal, additional, and Volff, Jean-Nicolas, additional
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- 2016
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20. Virus-derived DNA drives mosquito vector tolerance to arboviral infection
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Goic, Bertsy, primary, Stapleford, Kenneth A., additional, Frangeul, Lionel, additional, Doucet, Aurélien J., additional, Gausson, Valérie, additional, Blanc, Hervé, additional, Schemmel-Jofre, Nidia, additional, Cristofari, Gael, additional, Lambrechts, Louis, additional, Vignuzzi, Marco, additional, and Saleh, Maria-Carla, additional
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- 2016
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21. Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts
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Albrengues, Jean, primary, Bertero, Thomas, additional, Grasset, Eloise, additional, Bonan, Stephanie, additional, Maiel, Majdi, additional, Bourget, Isabelle, additional, Philippe, Claude, additional, Herraiz Serrano, Cecilia, additional, Benamar, Samia, additional, Croce, Olivier, additional, Sanz-Moreno, Victoria, additional, Meneguzzi, Guerrino, additional, Feral, Chloe C., additional, Cristofari, Gael, additional, and Gaggioli, Cedric, additional
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- 2015
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22. Nucleic Acid Chaperone Activity of the Yeast Ty3 Retrotransposon Nucleocapsid Protein
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Chaurasiya, Kathy R., primary, Geertsema, Hylkje, additional, Wang, Fei, additional, Cristofari, Gael, additional, Darlix, Jean-Luc, additional, and Williams, Mark, additional
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- 2010
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23. The tumor suppressor microRNA let-7 inhibits human LINE-1 retrotransposition
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Suyapa Amador-Cubero, Sebastien Viollet, Laura Sánchez, Alejandro Rubio-Roldan, Pablo Tristan-Ramos, Sara R. Heras, Gaël Cristofari, Guillermo Peris, [Tristán-Ramos,P, Rubio-Roldan,A, Peris,G, Sánchez,L, Amador-Cubero,S, Heras,SR] GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government. PTS Granada, Granada, Spain. [Tristán-Ramos,P, Heras,SR] Dept. Biochemistry and Molecular Biology II, Faculty of Pharmacy, University of Granada, Granada, Spain. [Peris,G] Dept. of Computer Languages and Systems, Universitat Jaume I, Castellón de la Plana, Spain. [Viollet,S, Cristofari,G] Université Côte d’Azur, CNRS, INSERM, IRCAN, Nice, France., The work in the lab of G.C. was supported by the European Research Council (ERC-2009-StG 243312, Retrogenomics), by the French Government (National Research Agency, ANR) through the 'Investments for the Future' programs LABEX SIGNALIFE ANR-11-LABX-0028-01 and IDEX UCAJedi ANR-15-IDEX-01, by CNRS (GDR 3546), and by the University Hospital Federation (FHU) OncoAge.This article is part of the doctoral thesis of P.T.-R., a graduate student in the PhD programme of Biomedicine at the University of Granada, who was supported by MINECO (PEJ-2014-A-31985 and SAF2015-71589-P). S.R.H. is funded by MINECO cofounding by European Regional Development Fund (SAF2015-71589-P), Ramón y Cajal (RYC-2016-21395) and a Career Integration Grant-Marie Curie (FP7-PEOPLE-2011-CIG-303812)., Universidad de Granada = University of Granada (UGR), Centre for Genomics and Oncological Reearch (GENYO), Universitat Jaume I, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), European Project, European Project: 303812,EC:FP7:PEOPLE,FP7-PEOPLE-2011-CIG,L1-DIGEORGESYNDROME(2012), Cristofari, Gael, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Idex UCA JEDI - - UCA JEDI2015 - ANR-15-IDEX-0001 - IDEX - VALID, ERC number 243312, Retrogenomics - INCOMING, Role of LINE-1 retrotransposons in the human disease DiGeorge Syndrome - L1-DIGEORGESYNDROME - - EC:FP7:PEOPLE2012-06-01 - 2016-11-21 - 303812 - VALID, University of Granada [Granada], and Université Nice Sophia Antipolis (... - 2019) (UNS)
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0301 basic medicine ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Nucleotidyltransferases::DNA Nucleotidyltransferases::DNA-Directed DNA Polymerase::RNA-Directed DNA Polymerase [Medical Subject Headings] ,Lung Neoplasms ,Somatic cell ,General Physics and Astronomy ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Endonucleases [Medical Subject Headings] ,Retrotransposon ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::RNA, Small Untranslated::MicroRNAs [Medical Subject Headings] ,Non-coding RNAs ,law.invention ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,0302 clinical medicine ,Lung neoplasms ,law ,Tumor Cells, Cultured ,Transposition ,Genes, Tumor Suppressor ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Untranslated::Untranslated Regions::3' Untranslated Regions [Medical Subject Headings] ,Carcinoma de células escamosas ,lcsh:Science ,3' Untranslated Regions ,Cancer genetics ,MicroARNs ,0303 health sciences ,Multidisciplinary ,RNA-Directed DNA Polymerase ,Anatomy::Cells::Cells, Cultured::Tumor Cells, Cultured [Medical Subject Headings] ,Translation (biology) ,3. Good health ,Cell biology ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Transposable element ,Neoplasias pulmonares ,Science ,Carcinoma, squamous cell ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Adenocarcinoma of Lung ,Biology ,Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings] ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression::Protein Biosynthesis [Medical Subject Headings] ,Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell [Medical Subject Headings] ,microRNA ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,RNA, Messenger ,Genes Supresores de Tumor ,030304 developmental biology ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Genes, Recessive::Genes, Tumor Suppressor [Medical Subject Headings] ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Binding Sites ,Whole Genome Sequencing ,Oncogene ,Genes, tumor suppressor ,General Chemistry ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites [Medical Subject Headings] ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger [Medical Subject Headings] ,Endonucleases ,Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, Neoplastic [Medical Subject Headings] ,Long interspersed nuclear element ,MicroRNAs ,030104 developmental biology ,Long Interspersed Nucleotide Elements ,Phenomena and Processes::Genetic Phenomena::Genetic Structures::Base Sequence::Repetitive Sequences, Nucleic Acid::Interspersed Repetitive Sequences::Retroelements::Long Interspersed Nucleotide Elements [Medical Subject Headings] ,Protein Biosynthesis ,Suppressor ,lcsh:Q ,Human genome - Abstract
Nearly half of the human genome is made of transposable elements (TEs) whose activity continues to impact its structure and function. Among them, Long INterspersed Element class 1 (LINE-1 or L1) elements are the only autonomously active TEs in humans. L1s are expressed and mobilized in different cancers, generating mutagenic insertions that could affect tumor malignancy. Tumor suppressor microRNAs are ∼22nt RNAs that post-transcriptionally regulate oncogene expression and are frequently downregulated in cancer. Here we explore whether they also influence L1 mobilization. We show that downregulation of let-7 correlates with accumulation of L1 insertions in human lung cancer. Furthermore, we demonstrate that let-7 binds to the L1 mRNA and impairs the translation of the second L1-encoded protein, ORF2p, reducing its mobilization. Overall, our data reveals that let-7, one of the most relevant microRNAs, maintains somatic genome integrity by restricting L1 retrotransposition., European Research Council (ERC) ERC-2009-StG 243312, French National Research Agency (ANR) ANR-11-LABX-0028-01 ANR-15-IDEX-01, Centre National de la Recherche Scientifique (CNRS) 3546, University Hospital Federation (FHU) OncoAge, MINECO PEJ-2014-A-31985 SAF2015-71589-P, MINECO by European Regional Development Fund SAF2015-71589-P, Spanish Government RYC-2016-21395, Career Integration Grant-Marie Curie FP7-PEOPLE-2011-CIG-303812
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- 2020
24. Flip-flop genomics: Charting inversions in the human population
- Author
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Gael Cristofari, Sophie LANCIANO, Cristofari, Gael, Idex UCA JEDI - - UCA JEDI2015 - ANR-15-IDEX-0001 - IDEX - VALID, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères - - ImpacTE2019 - ANR-19-CE12-0032 - AAPG2019 - VALID, Activités et diversité des rétrotransposons L1 naturels dans les génomes humains - - ActiveLINE2021 - ANR-21-CE12-0001 - AAPG2021 - VALID, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Fondation pour la Recherche Medicale (FRM, DEQ20180339170), Inserm (GOLD cross-cutting program on genomic variability), Centre National de la Recherche Scientifique (CNRS GDR 3546)., ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-19-CE12-0032,ImpacTE,Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères(2019), and ANR-21-CE12-0001,ActiveLINE,Activités et diversité des rétrotransposons L1 naturels dans les génomes humains(2021)
- Subjects
Gene Rearrangement ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,structural variants ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,General Biochemistry, Genetics and Molecular Biology ,LINE-1 ,premutational states ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,genomics ,Humans ,inversions ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,genetics ,health care economics and organizations ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Detecting large genomic inversions has long been challenging. In a new study, Porubsky et al. resolve these complex rearrangements in 41 individuals and discover wide regions that undergo recurrent inversions, some of which even toggle back and forth (Porubsky et al., 2022). Many of these regions are associated with genomic disorders.
- Published
- 2022
25. Locus-specific chromatin profiling of evolutionarily young transposable elements
- Author
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Darren Taylor, Robert Lowe, Claude Philippe, Kevin C. L. Cheng, Olivia A. Grant, Nicolae Radu Zabet, Gael Cristofari, Miguel R. Branco, Barts & The London School of Medicine and Dentistry [London, UK] (Blizard Institute), Queen Mary University of London (QMUL), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-16-CE12-0020,RETROMET,Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée.(2016), ANR-19-CE12-0032,ImpacTE,Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères(2019), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Cristofari, Gael, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée. - - RETROMET2016 - ANR-16-CE12-0020 - AAPG2016 - VALID, and Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères - - ImpacTE2019 - ANR-19-CE12-0032 - AAPG2019 - VALID
- Subjects
Transposable element ,[SDV]Life Sciences [q-bio] ,Interspersed repeat ,Locus (genetics) ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Computational biology ,Biology ,Genome ,03 medical and health sciences ,Mice ,0302 clinical medicine ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Genetics ,Animals ,Humans ,Epigenetics ,Epigenomics ,030304 developmental biology ,Regulation of gene expression ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Genomics ,Repetitive dna ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Chromatin ,[SDV] Life Sciences [q-bio] ,Gene Expression Regulation ,Epigenetics and chromatin ,DNA Transposable Elements ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Transposable elements ,030217 neurology & neurosurgery - Abstract
Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein–DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of HiChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we reveal previously unappreciated variation in the epigenetic profiles of young TE loci in mouse and human cells. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.
- Published
- 2021
26. Novel PCR-based assay to detect and characterize LINE-1 retrotransposition in human cancers
- Author
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Pradhan, Barun, University of Helsinki, Faculty of Medicine, Doctoral Programme in Biomedicine, Helsingin yliopisto, lääketieteellinen tiedekunta, Biolääketieteellinen tohtoriohjelma, Helsingfors universitet, medicinska fakulteten, Doktorandprogrammet i biomedicin, Cristofari, Gael, and Kauppi, Liisa
- Subjects
molekylärbiologi ,molecular biology ,molekyylibiologia - Abstract
Transposable elements (TEs) comprise almost half of the human genome because of their mobile activity during genome evolution. Although most families of TE are currently inactive in the human genome, one young TE family called Long Interspersed Nuclear Element (LINE)-1 is found to be active in germ cells, during embryonic development, and in diseases such as cancer, especially epithelial cancer types. LINE-1 is an RNA transposon (retrotransposon) which means it moves from one genomic location to another via an RNA intermediate by a process called retrotransposition. By following this replicative cycle, LINE-1 has already made more than 500,000 near-identical copies of itself and hence occupied 17% of the human genome. However, most of these copies have accumulated inactivating mutations and/or truncations and are retrotransposition-incompetent. The diploid genome in an individual is estimated to have only 80-100 potentially active LINE-1s. These potentially active LINE-1s are epigenetically silenced in normal cells. Widespread epigenetic modification during cancer alters this silencing mechanism and activates these LINE-1s which have the potential to generate mutagenic insertions in the genome. Detection of de novo LINE-1 insertions among more than 500,000 pre-existing LINE-1 copies remains challenging. To address this unmet need, we developed a novel PCR-based method that detects de novo insertions originating from one of the most active LINE-1 loci in the human genome (located within the TTC28 gene, hereafter referred to as TTC28 LINE-1). Compared to whole-genome sequencing (WGS), this approach is substantially more sensitive, identifying nearly three times more de novo TTC28 LINE-1 insertions in two colorectal cancer samples. Moreover, by taking advantage of long-read single-molecule sequencing, we were able to characterize de novo LINE-1 insertions in their entirety at nucleotide-level resolution. Using uterine leiomyoma as the disease model, we show that LDI-PCR is also suited for detecting DNA rearrangements in rearrangement-prone genomic regions with high sensitivity. Next, we traced the activity of TTC28 LINE-1 in a panel of ten high-grade serous ovarian carcinoma (HGSOC) cell lines, five of which were proficient for homologous recombination (HR), an error-free DNA double-strand break repair pathway, and the other five were HR-deficient. Although TTC28 LINE-1 mRNA was expressed in all HGSOC cell lines, HR-proficient HGSOC cell lines showed a higher frequency of de novo TTC28 LINE-1 insertions in comparison to HR-deficient cell lines. We speculate that the simultaneous loss of HR-mediated DNA repair and gain of LINE-1 activity (which generates DNA double-strand breaks as part of the insertional process) could be detrimental to HR-deficient cell lines. HR-proficient cell lines, in contrast, might tolerate LINE-1 activity and thus have accrued more de novo LINE-1 insertions. Altogether, this thesis provides a highly sensitive method to detect and characterize de novo LINE-1 retrotransposition events. By employing this approach, this thesis also demonstrates that LINE-1 retrotransposition is more frequent in HGSOC cell lines that are proficient in repairing DNA double-strand breaks by the HR pathway. Puolet ihmisen perimästä koostuu liikkuvista DNA-elementeistä, eli transposoneista. Vaikka useimmat näistä eivät enää ole aktiivisia ihmisen genomissa, evolutiivisesti nuori transposoniperhe nimeltään LINE-1 (Long Interspersed Nuclear Element) on aktiivinen ituradan soluissa, sikiön kehityksen aikana sekä erityisesti epiteeliperäisissä syövissä. LINE-1 on RNA-transposoni (retrotransposoni), eli se kopioi itsensä perimän DNA:sta RNA-välivaiheen kautta takaisin DNA:ksi. Ihmisen genomissa on yli puoli miljoonaa lähes samanlaista LINE-1-kopiota, mikä on noin 17 % koko perimästä. Suurin osa näistä on kuitenkin kerryttänyt mutaatioita, eivätkä ne enää ole aktiivisia. Arviolta 80–100 näistä LINE-1-elementeistä ovat aktiivisia, mutta normaaleissa soluissa hiljennetty epigeneettisin mekanismein. Syöpäsoluissa tämä epigeneettinen säätely on usein häiriintynyt, mikä voi johtaa LINE-1-elementtien aktivoitumiseen ja siten mahdollisiin vahingollisiin insertioihin genomissa. Uusien LINE-1-insertioiden havaitseminen yli 500 000 LINE-1-kopion joukosta on edelleen haastavaa. Olemme kehittäneet uuden, PCR-pohjaisen menetelmän (LDI-PCR) tämän ongelman ratkaisemiseksi. Menetelmä tunnistaa uudet insertiot, jotka ovat lähtöisin yhdestä ihmisgenomin aktiivisimmista, TTC28-geenissä sijaitsevasta LINE-1-elementistä (TTC28-LINE-1). Verrattuna koko genomin sekvensointiin PCR-pohjainen menetelmä on tarkempi ja tunnistaa lähes kolme kertaa enemmän TTC28 LINE-1 insertioita. Yhdistettynä pitkien yksittäisen DNA-jaksojen sekvensointiin pystyimme karakterisoimaan LINE-1 insertiot kokonaisuudessaan yhden emäsparin tarkkuudella. LDI-PCR kykenee tunnistamaan ja karakterisoimaan myös erilaisia genomin uudelleenjärjestäytymisiä, minkä osoitimme kohdun hyvälaatuisissa kasvaimissa, leiomyoomissa. Tutkimme TTC28-LINE-1:n aktiivisuutta käyttäen LDI-PCR:ää kymmenestä eri munasarjasyövän soluviljelmistä. Näistä puolella oli toimimaton DNA:n korjauskoneisto, jota kutsutaan homologiseksi rekombinaatioksi (HR). Toimimaton HR-koneisto johtaa DNA:n kaksoisjuostekatkoksien kertymiseen genomissa, mikä on vahingollista soluille. TTC28-LINE-1 mRNA:ta löytyi kaikista tutkituista näytteistä, mutta näytteistä, joissa oli toimiva HR-koneisto, löytyi enemmän uusia TTC28 LINE-1 insertioita verrattuna näytteisiin, joissa ei ollut toimivaa HR-koneistoa. LINE-1 elementin aktivoituminen, joka luo katkoksia DNA:n kaksoisjuosteeseen yhdistettynä toimimattomaan HR-koneistoon luo saattaa olosuhteet, jotka ovat tappavan vahingollisia soluille. Toimiva HR-koneisto taas voi suojata solua näitä LINE-1-elementtien luomia katkoksia vastaan, mikä auttaa LINE-1 jaksoja liikkumaan ja insertoitumaan ilman vahingollisia mutaatioita DNA:ssa ja siten johtaa uusien LINE-1-insertioiden kertymiseen soluissa. Tämä väitöskirja esittelee menetelmän, jolla voidaan karakterisoida ja kartoittaa uusien LINE-1-elementtien insertioita ihmisgenomissa. Hyödyntäen väitöskirjassa kuvattua lähestymistapaa osoitimme LINE-1 insertioiden olevan yleisempiä munasarjasyövän soluviljelmissä, joilla on toimiva HR-koneisto ja siten kyky korjata DNA:n kaksoisjuostekatkoksia. Julkaistu painettuna: Helsinki: Unigrafia, 2021
- Published
- 2021
27. Nascent RNA m(6)A modification at the heart of the gene–retrotransposon conflict
- Author
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Victor Billon, Gaël Cristofari, Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Work in the laboratory of GC is supported by the French government, through the Agence Nationale de la Recherche (Idex UCAJEDI, ANR-15-IDEX-01, Labex SIGNALIFE, ANR-11-LABX-0028-01, RetroMet, ANR-16-CE12-0020, ImpacTE, ANR-19-CE12-0032), the Fondation pour la Recherche Médicale (FRM, DEQ20180339170), Inserm (GOLD cross-cutting programme on genomic variability), CNRS (GDR 3546), and the University Hospital Federation (FHU) OncoAge., ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-16-CE12-0020,RETROMET,Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée.(2016), ANR-19-CE12-0032,ImpacTE,Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères(2019), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Cristofari, Gael, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée. - - RETROMET2016 - ANR-16-CE12-0020 - AAPG2016 - VALID, Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères - - ImpacTE2019 - ANR-19-CE12-0032 - AAPG2019 - VALID, and Idex UCA JEDI - - UCA JEDI2015 - ANR-15-IDEX-0001 - IDEX - VALID
- Subjects
0303 health sciences ,business.industry ,RNA ,Retrotransposon ,Cell Biology ,Computational biology ,Biology ,Research Highlight ,03 medical and health sciences ,0302 clinical medicine ,Text mining ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,business ,Molecular Biology ,Gene ,030217 neurology & neurosurgery ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology - Abstract
International audience; No abstract available
- Published
- 2021
28. Measuring and interpreting transposable element expression
- Author
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Sophie Lanciano, Gaël Cristofari, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), This work was supported by grants to G.C. from the Fondation pour la Recherche Médicale (DEQ20180339170), the Agence Nationale de la Recherche (LABEX SIGNALIFE, ANR-11-LABX-0028-01, RetroMet, ANR-16-CE12-0020, ImpacTE, ANR-19-CE12-0032), the Canceropôle Provence–Alpes–Côte d’Azur, the French National Cancer Institute (INCa) and the Provence–Alpes–Côte d’Azur Region, CNRS (GDR 3546), and the University Hospital Federation (FHU) OncoAge., ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-16-CE12-0020,RETROMET,Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée.(2016), ANR-19-CE12-0032,ImpacTE,Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères(2019), Cristofari, Gael, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Rendre unique l'ADN répété ou comment révéler la régulation épigénétique des rétrotransposons L1 dans les cellules somatiques humaines à une résolution inégalée. - - RETROMET2016 - ANR-16-CE12-0020 - AAPG2016 - VALID, Réseau de régulation et élément LINE-1 : impact global des éléments transposables récents sur l'activité génique chez les Mammifères - - ImpacTE2019 - ANR-19-CE12-0032 - AAPG2019 - VALID, and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
- Subjects
Transposable element ,Transcription, Genetic ,[SDV]Life Sciences [q-bio] ,Gene Expression ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Computational biology ,Biology ,Genome ,DNA sequencing ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Transcription (biology) ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Gene expression ,Genetics ,Animals ,Humans ,Molecular Biology ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Polymorphism, Genetic ,Plants ,Chromatin ,[SDV] Life Sciences [q-bio] ,DNA Transposable Elements ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Mobile genetic elements ,030217 neurology & neurosurgery - Abstract
Transposable elements (TEs) are insertional mutagens that contribute greatly to the plasticity of eukaryotic genomes, influencing the evolution and adaptation of species as well as physiology or disease in individuals. Measuring TE expression helps to understand not only when and where TE mobilization can occur but also how this process alters gene expression, chromatin accessibility or cellular signalling pathways. Although genome-wide gene expression assays such as RNA sequencing include transposon-derived transcripts, most computational analytical tools discard or misinterpret TE-derived reads. Emerging approaches are improving the identification of expressed TE loci and helping to discriminate TE transcripts that permit TE mobilization from chimeric gene–TE transcripts or pervasive transcription. Here we review the main challenges associated with the detection of TE expression, including mappability, insertional and internal sequence polymorphisms, and the diversity of the TE transcriptional landscape, as well as the different experimental and computational strategies to solve them. Computational tools to analyse RNA sequencing data often disregard or even misinterpret reads derived from transposable elements. This Review highlights the main challenges associated with the detection of transposable element expression, including mappability, sequence polymorphisms and transcript diversity, and discusses the experimental and computational strategies to overcome them.
- Published
- 2020
29. Locus-specific chromatin profiling of evolutionarily young transposable elements.
- Author
-
Taylor D, Lowe R, Philippe C, Cheng KCL, Grant OA, Zabet NR, Cristofari G, and Branco MR
- Subjects
- Animals, Gene Expression Regulation, Genomics, Humans, Mice, Chromatin genetics, DNA Transposable Elements genetics
- Abstract
Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of HiChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we reveal previously unappreciated variation in the epigenetic profiles of young TE loci in mouse and human cells. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2022
- Full Text
- View/download PDF
30. The OncoAge Consortium: Linking Aging and Oncology from Bench to Bedside and Back Again.
- Author
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Hofman P, Ayache N, Barbry P, Barlaud M, Bel A, Blancou P, Checler F, Chevillard S, Cristofari G, Demory M, Esnault V, Falandry C, Gilson E, Guérin O, Glaichenhaus N, Guigay J, Ilié M, Mari B, Marquette CH, Paquis-Flucklinger V, Prate F, Saintigny P, Seitz-Polsky B, Skhiri T, Van Obberghen-Schilling E, Van Obberghen E, and Yvan-Charvet L
- Abstract
It is generally accepted that carcinogenesis and aging are two biological processes, which are known to be associated. Notably, the frequency of certain cancers (including lung cancer), increases significantly with the age of patients and there is now a wealth of data showing that multiple mechanisms leading to malignant transformation and to aging are interconnected, defining the so-called common biology of aging and cancer. OncoAge, a consortium launched in 2015, brings together the multidisciplinary expertise of leading public hospital services and academic laboratories to foster the transfer of scientific knowledge rapidly acquired in the fields of cancer biology and aging into innovative medical practice and silver economy development. This is achieved through the development of shared technical platforms (for research on genome stability, (epi)genetics, biobanking, immunology, metabolism, and artificial intelligence), clinical research projects, clinical trials, and education. OncoAge focuses mainly on two pilot pathologies, which benefit from the expertise of several members, namely lung and head and neck cancers. This review outlines the broad strategic directions and key advances of OncoAge and summarizes some of the issues faced by this consortium, as well as the short- and long-term perspectives.
- Published
- 2019
- Full Text
- View/download PDF
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