ARN non codants, épigénétique et stabilité génomique

  • Les éléments transposables (ETs) sont des séquences d’ADN répétées capables de se multiplier en insérant de nouvelles copies dans le génome qu’elles parasitent. L’hôte se défend contre ces envahisseurs grâce à un phénomène d’immunité qui a été découvert très récemment et qui est très conservé dans tout le monde vivant, des bactéries aux animaux. Au cœur de ce mécanisme, le RISC (RNA-interfering silencing complex) résulte de l’association d’une des protéines de la famille Argonaute avec un petit ARN non codant qui la guide vers sa cible ARN par homologie de séquence. Le ciblage d’un ARN messager dans le cytoplasme provoque généralement sa dégradation (post-transcriptional gene silencing : PTGS) tandis qu’on observe plutôt une répression épigénétique (transcriptional gene silencing : TGS) quand un ARN naissant est ciblé par le RISC dans le noyau.
    Notre groupe s’intéresse à la biogenèse et la fonction des complexes piRISC composé de piARN (Piwi-associated small RNAs) et d’une protéine Argonaute dans le modèle Drosophile. Ces piARN sont codés par des loci hétérochromatiniens appelés « piRNA clusters ».

    Figure 1
    Biogenèse et role des piARN dans les cellules germinales de Drosophile

    Nous avons notamment montré que la protéine Argonaute Piwi est requise de façon transitoire pendant le développement embryonnaire pour y déposer une marque hétérochromatinienne essentielle (triméthylation de la lysine 9 de l’histone H3) qui sera ensuite maintenue pendant tout le reste du développement.

    Figure 2

    Au laboratoire, nous utilisons les dernières approches de séquençage à haut débit (small RNA-seq, RNA-seq, ChIP-seq) et de protéomique (spectrométrie de masse), combinées avec des outils de génétique et de biologie cellulaire et moléculaire (CRISPR/dCas9) afin d’étudier le rôle complexe des piRISC.


    A ce jour, notre recherche est financée par :

    logo arc

    Membres

    Eugenia Basyuk
    Basyuk Eugenia
    Severine Chambeyron
    Chambeyron Severine
    Alain Pelisson
    Pelisson Alain
    Céline Franckhauser
    Franckhauser Céline
    Bruno Mugat
    Mugat Bruno
    Christophe Jourdan
    Jourdan Christophe
    Simon Nicot
    Nicot Simon
    Megane Da Silva Bizouard
    Da Silva Bizouard Megane

    Publications

    The somatic piRNA pathway controls germline transposition over generations.

    Barckmann B, El-Barouk M, Pélisson A, Mugat B, Li B, Franckhauser C, Fiston Lavier AS, Mirouze M, Fablet M, Chambeyron S

    2018 - Nucleic Acids Res, 46(18):9524-9536

    Demander l'article complet30312469

    Identification of misexpressed genetic elements in hybrids between Drosophila-related species

    Lopez-Maestre H, Carnelossi EA, Lacroix V, Burlet N, Mugat B, Chambeyron S, Carareto CM, Vieira C

    2017 - Sci Rep., 7, 40618

    Demander l'article complet28091568

    Piwi Is Required during Drosophila Embryogenesis to License Dual-Strand piRNA Clusters for Transposon Repression in Adult Ovaries

    Akkouche, A., Mugat, B., Barckmann, B., Varela-Chavez, C., Li, B., Raffel, R., Pelisson, A., Chambeyron, S.

    2017 - Molecular Cell, 66, 3, 411-419

    Demander l'article complet28457744

    Transposable Element Misregulation Is Linked to the Divergence between Parental piRNA Pathways in Drosophila Hybrids

    Romero-Soriano V, Modolo L, Lopez-Maestre H, Mugat B, Pessia E, Chambeyron S, Vieira C, Garcia Guerreiro MP

    2017 - Genome Biol Evol., 9(6):1450-1470

    Demander l'article complet28854624
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    Publications de l'équipe

  • The Chambeyron lab is interested in piRNAs and TE biology. Our aim is to provide molecular explanations for the biological processes that underlie or are controlled by the piRNA pathway. We combine four different research topics:

    Figure 3

    As gardians of genome: Study the real impact of piRISC depletion on TE mobilisation

    The piRNA pathway is generally accepted as the major TE regulator in Drosophila germ line, but the real impact of piRNA pathway loss on TE behavior was never shown. We want to understand the real impact of piRNA pathway loss on TE transposition and genome integrity. We use a conditional somatic Piwi knockdown in Drosophila ovaries to study TE behavior in a piRNA pathway loss situation and the effect of TE activation on genome integrity.

    Overexpression of piRISC reported in many cancers: Cause or consequences ?

    Studies of the role of the piRNA pathway in cancer has become an emerging field since several links between piRNA pathway deregulation and cancer were reported. piRNA overexpression was demonstrated in several cancer tissues including testis, lung, colon, breast. In the lab, we would like to perform functional studies to demonstrate some causal relationships between piRNA pathway deregulation and cancer.

    In constitutive heterochromatin formation: Genome partitioning

    We demonstrated recently that Piwi is necessary in the early embryo to license piRNA cluster for piRNA production. After this initial cluster licensing Piwi is dispensable for cluster maintenance. Cluster licensing happens during the time of general heterochromatin establishment in the embryo. We are now studying a potential implication of Piwi on the establishment of constitutive heterochromatin.

    In facultative heterochromatin formation: TE transcriptional repression

    One way the piRNA pathway regulates TEs in the germline is a Piwi-dependent transcriptional repression mechanism: Piwi-loaded piRNAs enter in the nucleus and bind, guided by its piRNAs, to nascent TE transcripts. This leads to heterochromatin formation by H3K9 trimethylation and HP1 binding. One big open question is how Piwi binding to the TE transcript leads to changes in chromatin state. We use biochemical approaches to identify the different subunits of the repressor complex.

  • Research Director working on “Non-coding RNA, epigenetics and genome stability”
    Scientific Focus Areas: piRNA, chromatin, epigenetics, transposable elements, bio-informatics

    Education

    2011 - HDR, University of Montpellier I (France)
    2002 - Ph.D. in Molecular Biology and Genetics - University of Montpellier II (France)
    1998 - Master II - University of Montpellier I, (France)

    Research Experience

    2010-present - Group Leader (DR2) of Non-coding RNA, epigenetics and genome stability at IGH CNRS-UMR9002 (Montpellier, France).
    2005-2009 - Project Leader (CR2) at IGH CNRS (Montpellier, France).
    2002-2005 - Post-doctoral research associate at the MRC (Edinburgh, UK) in Prof. W. Bickmore lab.
    1998-2002 - PhD studentship at IGH CNRS (Montpellier, France) in Dr. A. Bucheton lab.

    Training activities

    • 2 PhD students supervision: T. Grentzinger (2010 - July 2013); M. El Barouk (2013 - December 2016)
    • 4 post-docs: Dr V. Serrano (2010-2012) ; Dr C. Varela Chavez (2014-2016) ; Dr A. Akkouche (2013-2016) ; Dr B. Barckmann (2016-2017)
    • 4 engineers since 2010: B. Mugat, C. Brun, C. Armenise and B. Li
    • Master students’ lab training (1 per year since 2010)
    • Teaching graduate students at French and European Universities every year (Paris, Montpellier and Zurich)

    Addition Scientific Activities

    2017 - Co-organizer of a symposium for the 20 years of the IGH
    2015 - Co-organizer International Congres of Transposable Elements, Saint Malo, France
    2015 - Co-organizer 29th French Drosophila Conference - Presqu’île du Ponant, France
    2013 - Co-organizer of National Congres of Transposable Element”, Montpellier, France

    Fellowships and awards

    2016-present - Prime d’Excellence Scientifique, CNRS.

    Current Grants:

    2016-2017 - Partenariats Hubert Curien (PHC) PROCOPE 2017: Echange Allemagne – France.
    2015-2017 - Fondation Cancer (ARC): Subvention.
    2014-2017 - Fondation pour la Recherche Médicale (FRM): Programme Epigénétique « DEP20131128518 »

    Previous Grants:

    2013-2016 - Fondation ARC: Post-doctoral fellowship
    2010-2014 - National Research Agency (ANR)
    2010-2012 - Fondation pour la Recherche Médicale (FRM): Fellowship for a Bioinformatician
    2009-2011 - Association pour la Recherche sur le Cancer (ARC): Subvention fixe
    2009-2012 - Sequencing project by the GIS IBiSA Génoscope, Paris