Team 04: Genetic instabilities and control by the host genome

Our research focuses on the mechanisms allowing a balance between repression and mobilization of transposable elements

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Research

Transposable elements (TE), these DNA sequences having the ability to move to new sites in genomes, are major genomic components. In Drosophila melanogaster, they comprise almost 20% of the genome while in human, the sole family of retrotransposons that move through an RNA intermediate in a process termed retrotransposition, comprises more than 40 % of the genome. TE activity represents a constant threat for the stability of eukaryotic genomes and, therefore, protection mechanisms have evolved that limit their mobilization. Nonetheless, TEs have colonized genomes efficiently and are thus thought to provide evolutionary advantages through their effects on genome expression and dynamics. Therefore, TEs have some capacity to bypass host defense mechanisms and mobilize in cells that will ensure their propagation to the next generation

Our research focuses on the mechanisms allowing a balance between TE repression and mobilization. To this goal, we work on Drosophila melanogaster and combine genetic approaches, molecular and cellular biology as well as transgenesis and genome wide analyses.

We are investigating three specific features of this control:

  1. Silencing mechanisms controlling TE: We are investigating the molecular mechanisms and actors involved in the multiple pathways of the genomic defense acting against TE invasions. Their spatio-temporal specificities and plasticity are examined as well as strategies allowing these silencing to exert their effect on the progeny.
  2. Role of heterochromatic regions: We are investigating the role of heterochromatic regions and focus our study on their control of transposable elements. Heterochromatic loci producing small RNAs and called piRNA clusters such as the flamenco locus (or COM locus) are more particularly examined through the analysis of their molecular structure and dynamics, their transcriptional control, their nuclear localization, and their evolutive history.
  3. Impact of transposable elements on the structural and functional organization of the genome: Due to their regulatory sequences and to specific chromatin structures associated to their insertions, transposable elements and their regulatory loci can be considered as creative forces directly contributing to genome regulation. Our goal is to unravel the relationship established between these sequences and their host genomes.

Overall, our study aims at gaining a deeper understanding of the silencing pathways used to control TE and their potential impact on the epigenetic regulation of eukaryotic genomes. Additionally, it aims at elucidating why a high amount of TE sequences is present in each genome while a strict control acts to restrict their invasion.

Financial supports:

                             

          

Research thematics

People

Last Name First Name Position Contact
Abdou AKKOUCHE profile picture AKKOUCHE Abdou Post-doctoral Fellow
Emilie BRASSET profile picture BRASSET Emilie Principal Investigator
Mathilde CONSTANTIN profile picture CONSTANTIN Mathilde Intern
Mathilde CONSTATIN profile picture CONSTATIN Mathilde Intern
Nathalie GUEGUEN profile picture GUEGUEN Nathalie Research Technician
Silke JENSEN profile picture JENSEN Silke Research Fellow
Aline MARTINS profile picture MARTINS Aline Ph.D Student
Stephanie MAUPETIT MEHOUAS profile picture MAUPETIT MEHOUAS Stephanie Research Engineer
Anaelle PATIN profile picture PATIN Anaelle Intern
Kateryna SVYRYDIVA profile picture SVYRYDIVA Kateryna Ph.D Student
Katerina SVYRYDOVA profile picture SVYRYDOVA Katerina Ph.D Student

Publications

  • 2021
    • S. Lamoine, M. Cumenal, D. Barriere, V. Pereira, M. Fereyrolles, L. Prival, J. Barbier, L. Boudieu, E. Brasset, B. Bertin, Y. Renaud, E. Miot-Noirault, M. Civiale, D. Balayssac, Y. Aissouni, A. Eschalier and J. Busserolles, “The Class I HDAC Inhibitor, MS-275, Prevents Oxaliplatin-Induced Chronic Neuropathy and Potentiates Its Antiproliferative Activity in Mice.”, International journal of molecular sciences, vol. 23 (1) , 2021.
    • A. Molla Herman and E. Brasset, “Rhino breaks the deadlock in Drosophila testis.”, PLoS Genet., vol. 17 (9) , pp. e1009702, 2021.
  • 2020
    • S. Jensen, E. Brasset, E. Parey, H. Roest Crollius, I. Sharakhov and C. Vaury, “Conserved Small Nucleotidic Elements at the Origin of Concerted piRNA Biogenesis from Genes and lncRNAs.”, Cells, vol. 9 (6) , 2020.
    • S. Maupetit-Mehouas and C. Vaury, “Transposon Reactivation in the Germline May Be Useful for Both Transposons and Their Host Genomes.”, Cells, vol. 9 (5) , 2020.
    • P. Komarov, O. Sokolova, N. Akulenko, E. Brasset, S. Jensen and A. Kalmykova, “Epigenetic Requirements for Triggering Heterochromatinization and Piwi-Interacting RNA Production from Transgenes in the Drosophila Germline.”, Cells, vol. 9 (4) , 2020.
  • 2019
    • C. Duc, M. Yoth, S. Jensen, N. Mouniee, C. Bergman, C. Vaury and E. Brasset, “Trapping a somatic endogenous retrovirus into a germline piRNA cluster immunizes the germline against further invasion.”, Genome biology, vol. 20 (1) , pp. 127, 2019.
    • K. Casier, V. Delmarre, N. Gueguen, C. Hermant, E. Viode, C. Vaury, S. Ronsseray, E. Brasset, L. Teysset and A. Boivin, “Environmentally-induced epigenetic conversion of a piRNA cluster.”, eLife, vol. 8 , 2019.
    • C. Dennis, E. Brasset and C. Vaury, “flam piRNA precursors channel from the nucleus to the cytoplasm in a temporally regulated manner along Drosophila oogenesis.”, Mob. DNA, vol. 10 , pp. 28, 2019.
  • 2018
    • E. Theron, S. Maupetit-Mehouas, P. Pouchin, L. Baudet, E. Brasset and C. Vaury, “The interplay between the Argonaute proteins Piwi and Aub within Drosophila germarium is critical for oogenesis, piRNA biogenesis and TE silencing.”, Nucleic Acids Res., 2018.
    • S. Maupetit-Mehouas, F. Court, C. Bourgne, A. Guerci-Bresler, P. Cony-Makhoul, H. Johnson, G. Etienne, P. Rousselot, D. Guyotat, A. Janel, E. Hermet, S. Saugues, J. Berger, P. Arnaud and M. Berger, “DNA methylation profiling reveals a pathological signature that contributes to transcriptional defects of CD34(+) CD15(-) cells in early chronic-phase chronic myeloid leukemia.”, Molecular oncology, vol. 12 (6) , pp. 814–829, 2018.
    • N. Akulenko, S. Ryazansky, V. Morgunova, P. Komarov, I. Olovnikov, C. Vaury, S. Jensen and A. Kalmykova, “Transcriptional and chromatin changes accompanying de novo formation of transgenic piRNA clusters.”, RNA, 2018.
    • R. Pogorelcnik, C. Vaury, P. Pouchin, S. Jensen and E. Brasset, “sRNAPipe: a Galaxy-based pipeline for bioinformatic in-depth exploration of small RNAseq data.”, Mob. DNA, vol. 9 , pp. 25, 2018.
  • 2017
    • A. Sarkar, J. Volff and C. Vaury, “piRNAs and their diverse roles: a transposable element-driven tactic for gene regulation?”, FASEB J., vol. 31 (2) , pp. 436–446, 2017.
  • 2016
    • C. Dennis, E. Brasset, A. Sarkar and C. Vaury, “Export of piRNA precursors by EJC triggers assembly of cytoplasmic Yb-body in Drosophila.”, Nature communications, vol. 7 , pp. 13739, 2016.
    • T. Bouschet, E. Dubois, C. Reynes, S. Kota, S. Rialle, S. Maupetit-Mehouas, M. Pezet, A. Le Digarcher, S. Nidelet, V. Demolombe, P. Cavelier, C. Meusnier, C. Maurizy, R. Sabatier, R. Feil, P. Arnaud, L. Journot and A. Varrault, “In Vitro Corticogenesis from Embryonic Stem Cells Recapitulates the In Vivo Epigenetic Control of Imprinted Gene Expression.”, Cerebral cortex (New York, N.Y. : 1991), 2016.
  • 2015
    • D. Homolka, R. Pandey, C. Goriaux, E. Brasset, C. Vaury, R. Sachidanandam, M. Fauvarque and R. Pillai, “PIWI Slicing and RNA Elements in Precursors Instruct Directional Primary piRNA Biogenesis.”, Cell Rep, 2015.
    • L. Veselovska, S. Smallwood, H. Saadeh, K. Stewart, F. Krueger, S. Maupetit-Mehouas, P. Arnaud, S. Tomizawa, S. Andrews and G. Kelsey, “Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape.”, Genome biology, vol. 16 (1) , pp. 209, 2015.
    • P. George, S. Jensen, R. Pogorelcnik, J. Lee, Y. Xing, E. Brasset, C. Vaury and I. Sharakhov, “Increased production of piRNAs from euchromatic clusters and genes in Anopheles gambiae compared with Drosophila melanogaster.”, Epigenetics & chromatin, vol. 8 , pp. 50, 2015.
  • 2014
    • R. Deplus, L. Blanchon, A. Rajavelu, A. Boukaba, M. Defrance, J. Luciani, F. Rothe, S. Dedeurwaerder, H. Denis, A. Brinkman, F. Simmer, F. Muller, B. Bertin, M. Berdasco, P. Putmans, E. Calonne, D. Litchfield, Y. de Launoit, T. Jurkowski, H. Stunnenberg, C. Bock, C. Sotiriou, M. Fraga, M. Esteller, A. Jeltsch and F. Fuks, “Regulation of DNA methylation patterns by CK2-mediated phosphorylation of Dnmt3a.”, Cell Rep, vol. 8 (3) , pp. 743–53, 2014.
    • C. Goriaux, E. Theron, E. Brasset and C. Vaury, “History of the discovery of a master locus producing piRNAs: the flamenco/COM locus in Drosophila melanogaster”, Front Genet, vol. 5 (257) , 2014.
    • R. Mteirek, N. Gueguen, S. Jensen, E. Brasset and C. Vaury, “Drosophila heterochromatin: structure and function.”, Current opinion in insect science, vol. 1 , pp. 19–24, 2014.
    • C. Goriaux, S. Desset, Y. Renaud, C. Vaury and E. Brasset, “Transcriptional properties and splicing of the flamenco piRNA cluster.”, EMBO Rep., vol. 15 (4) , pp. 411–8, 2014.
    • N. Parisot, A. Pelin, C. Gasc, V. Polonais, A. Belkorchia, J. Panek, H. El Alaoui, D. Biron, E. Brasset, C. Vaury, P. Peyret, N. Corradi, E. Peyretaillade and E. Lerat, “Microsporidian Genomes Harbor a Diverse Array of Transposable Elements that Demonstrate an Ancestry of Horizontal Exchange with Metazoans.”, Genome Biol Evol, vol. 6 (9) , pp. 2289–300, 2014.
    • E. Theron, C. Dennis, E. Brasset and C. Vaury, “Distinct features of the piRNA pathway in somatic and germ cells: from piRNA cluster transcription to piRNA processing and amplification.”, Mob. DNA, vol. 5 (1) , pp. 28, 2014.
    • J. Dufourt and C. Vaury, “During a short window of Drosophila oogenesis, piRNA biogenesis may be boosted and mobilization of transposable elements allowed.”, Front Genet, vol. 5 , pp. 385, 2014.
  • 2013
    • P. George, S. Jensen, C. Vaury and I. Sharakhov, “Organization and evolution of piRNA clusters in Anopheles gambiae”, Pathog Glob Health, vol. 107 (8) , pp. 428, 2013.
    • V. Zanni, A. Eymery, M. Coiffet, M. Zytnicki, I. Luyten, H. Quesneville, C. Vaury and S. Jensen, “Distribution, evolution, and diversity of retrotransposons at the flamenco locus reflect the regulatory properties of piRNA clusters.”, Proc. Natl. Acad. Sci. U.S.A., vol. 110 (49) , pp. 19842–7, 2013.
    • J. Dufourt, C. Dennis, A. Boivin, N. Gueguen, E. Theron, C. Goriaux, P. Pouchin, S. Ronsseray, E. Brasset and C. Vaury, “Spatio-temporal requirements for transposable element piRNA-mediated silencing during Drosophila oogenesis.”, Nucleic Acids Res., vol. 42 (4) , pp. 2512–24, 2013.
    • I. Olovnikov, S. Ryazansky, S. Shpiz, S. Lavrov, Y. Abramov, C. Vaury, S. Jensen and A. Kalmykova, “De novo piRNA cluster formation in the Drosophila germ line triggered by transgenes containing a transcribed transposon fragment.”, Nucleic Acids Res., vol. 41 (11) , pp. 5757–68, 2013.
    • J. Dufourt, P. Pouchin, P. Peyret, E. Brasset and C. Vaury, “NucBase, an easy to use read mapper for small RNAs.”, Mob. DNA, vol. 4 (1) , pp. 1, 2013.
    • C. Dennis, V. Zanni, E. Brasset, A. Eymery, L. Zhang, R. Mteirek, S. Jensen, Y. Rong and C. Vaury, “"Dot COM", a nuclear transit center for the primary piRNA pathway in Drosophila.”, PLoS ONE, vol. 8 (9) , pp. e72752, 2013.
    • E. Brasset and S. Chambeyron, “Epigenetics and transgenerational inheritance.”, Genome biology, vol. 14 (5) , pp. 306, 2013.
  • 2012
    • A. Ainouche, M. Betermier, M. Chandler, R. Cordaux, G. Cristofari, J. Deragon, P. Lesage, O. Panaud, H. Quesneville, C. Vaury, C. Vieira and C. Vitte, “International Congress on Transposable Elements (ICTE) 2012 in Saint Malo and the sea of TE stories.”, Mob. DNA, vol. 3 (1) , pp. 17, 2012.
  • 2011
  • 2009
    • E. Brasset, C. Hermant, S. Jensen and C. Vaury, “The Idefix enhancer-blocking insulator also harbors barrier activity.”, Gene, vol. 450 (1-2) , pp. 25–31, 2009.
    • M. Fablet, E. Lerat, R. Rebollo, B. Horard, N. Burlet, S. Martinez, E. Brasset, E. Gilson, C. Vaury and C. Vieira, “Genomic environment influences the dynamics of the tirant LTR retrotransposon in Drosophila.”, FASEB J., vol. 23 (5) , pp. 1482–9, 2009.
  • 2008
    • L. Guelen, L. Pagie, E. Brasset, W. Meuleman, M. Faza, W. Talhout, B. Eussen, A. de Klein, L. Wessels, W. de Laat and B. van Steensel, “Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions.”, Nature, vol. 453 (7197) , pp. 948–51, 2008.
    • S. Desset, N. Buchon, C. Meignin, M. Coiffet and C. Vaury, “In Drosophila melanogaster the COM locus directs the somatic silencing of two retrotransposons through both Piwi-dependent and -independent pathways.”, PLoS ONE, vol. 3 (2) , pp. e1526, 2008.
    • R. Palstra, M. Simonis, P. Klous, E. Brasset, B. Eijkelkamp and W. de Laat, “Maintenance of long-range DNA interactions after inhibition of ongoing RNA polymerase II transcription.”, PLoS ONE, vol. 3 (2) , pp. e1661, 2008.
    • B. Faye, F. Arnaud, E. Peyretaillade, E. Brasset, B. Dastugue and C. Vaury, “Functional characteristics of a highly specific integrase encoded by an LTR-retrotransposon.”, PLoS ONE, vol. 3 (9) , pp. e3185, 2008.