Non-coding RNA, epigenetics and genome stability


  • Over the past several years RNA-based immunity against genomic invaders has been discovered in all branches of life ranging from the CRISPR-Cas systems in bacteria to piRNAs in animals. piRNAs, in Drosophila germline cells are encoded by specific loci called piRNA clusters. These loci establish and maintain memory of “nonself ” by generating small guides to induce an adaptive defense against genomic parasites like transposable elements (TEs). At the heart of this defense mechanism resides a piRNA induced silencing complex (piRISC) which consists of a piRNA and its associated Argonaute protein partner. Within piRISC, the small RNA determines target specificity by base pairing, while its Argonaute partner governs effector activity. The mRNA can be either cleaved in the cytoplasm (PTGS) or bound in the nucleus leading to TGS.

    Figure 1
    Biogenesis and function of the piRNAs in Drosophila germline cells

    In the lab, we are dissecting the biogenesis and the role of piRISC in Drosophila. We have demonstrated that the Argonaute Piwi protein is required during Drosophila embryonic development for the activation of piRNA clusters via the deposition of H3K9me3 repressive marks. Once established in the embryo, this epigenetic mark will be maintained in a Piwi-independent manner during the whole ovarian development.

    Figure 1

    For our studies we combine fly genetics, proteomics and deep sequencing approaches (small RNA-seq, RNA-seq, ChIP-seq), using molecular and cell biology tools (CRISPR/dCas9).


    To date, our research is funded by:

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    Members

    Eugenia Basyuk
    Basyuk Eugenia
    Severine Chambeyron
    Chambeyron Severine
    Alain Pelisson
    Pelisson Alain
    Bruno Mugat
    Mugat Bruno
    Katell Audouin
    Audouin Katell
    Christophe Jourdan
    Jourdan Christophe
    Mourdas Mohamed
    Mohamed Mourdas
    Simon Nicot
    Nicot Simon
    Yuki Ogiyama
    Ogiyama Yuki
    Katrin Strobel
    Strobel Katrin

    Publications

    The Mi-2 nucleosome remodeler and the Rpd3 histone deacetylase are involved in piRNA-guided heterochromatin formation

    Bruno Mugat, Simon Nicot, Carolina Varela-Chavez, Christophe Jourdan, Kaoru Sato, Eugenia Basyuk, François Juge, Mikiko C. Siomi, Alain Pélisson & Séverine Chambeyron

    2020 - Nature Communications volume

    Request for full articleMore informations

    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

    Request for full article30312469

    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

    Request for full article28091568

    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

    Request for full article28457744
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    Publications of the team

  • 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