Programmed Genome Elimination


Our work aims to understand the fundamental mechanisms governing chromosome structure and genetic stability in eukaryotes. We study a remarkable process of genome editing that occurs during development in the unicellular eukaryote Paramecium.

Keywords: epigenetics, transposable elements, non-coding RNA, chromatin, Polycomb, genome evolution, Paramecium

+33 (0)157278009     sandra.duharcourt(at)      @DuharcourtLab

In Paramecium, at least one third of the germline genome is eliminated during development. This process involves the massive and reproducible elimination of repeated DNA sequences, such as transposable elements, and of 45,000 short non-coding sequences, scattered in the genome, relics of transposable elements. No conserved sequence motif that might serve as a specific recognition signal was identified among eliminated sequences. Understanding how such diverse sequences are recognized and excised remains challenging.

Current research aims to i) identify the eliminated sequences and describe their evolutionary trajectory, ii) elucidate the molecular mechanisms of programmed DNA elimination and iii) understand the possible functions associated with this massive genome reorganization.

The process involves small (s)RNA-directed heterochromatin formation and subsequent DNA excision and repair. sRNAs are produced from the germline genome during meiosis and guide the deposition of histone H3 post-translational epigenetic modifications (H3K9me3 and H3K27me3) onto sequences to be eliminated in the developing somatic nucleus, and specifically tether the DNA cleavage and repair machinery.

We demonstrated that the Paramecium histone methyltransferase Ezl1, a homolog of the mammalian PRC2 catalytic subunit, catalyzes H3K27me3 and H3K9me3 on TEs. We currently investigate how the Ezl1-associated complex is recruited to TEs, and how the histone H3 post-translational modifications trigger DNA cleavage and repair. We combine a large panel of molecular, cellular, high throughput sequencing, genetic and biochemical approaches to study the role of chromatin factors in the epigenetic control of DNA elimination.

Using an innovative flow cytometry approach to purify nuclei, we sequenced the genomes of nine Paramecium species for comparative genomics. These resources will allow us to elucidate the structure of Paramecium chromosomes, the evolutionary trajectories of eliminated sequences and their mechanisms of recognition and elimination.

Team leader

    01 57 27 80 09, room 554B


  • Louise ABBOU, Ingénieur technicien, DUHARCOURT LAB
    01 57 27 80 09, room 554B
  • Thomas BALAN, Doctorant, DUHARCOURT LAB
    01 57 27 80 00, room 554B
  • Olivia CHARMANT, Ingénieur technicien, DUHARCOURT LAB
    01 57 27 80 09, room 554B
  • Marina GIOVANNETTI, Stagiaire d études, DUHARCOURT LAB
  • Leticia KOCH LERNER, Enseignant Chercheur, DUHARCOURT LAB
    01 57 27 80 09, room 554B
  • Maud LAGIER, Stagiaire d études, DUHARCOURT LAB
    01 57 27 80 00
  • Cristina RUBIO RAMON, Ingénieur technicien, DUHARCOURT LAB
    01 57 27 80 09, room 554B

To contact a member of the team by e-mail:


Gout, J.-F., Hao, Y., Johri, P., Arnaiz, O., Doak, T. G., Bhullar, S., Couloux, A., Guérin, F., Malinsky, S., Potekhin, A., Sawka, N., Sperling, L., Labadie, K., Meyer, E., Duharcourt, S., & Lynch, M. (2023). Dynamics of Gene Loss following Ancient Whole-Genome Duplication in the Cryptic Paramecium Complex. Molecular Biology and Evolution, 40(5), msad107.
Hardy, A., Duharcourt, S., & Defrance, M. (2023). DNA Modification Patterns Filtering and Analysis Using DNAModAnnot. Methods in Molecular Biology (Clifton, N.J.), 2624, 87–114.
Miró-Pina, C., Charmant, O., Kawaguchi, T., Holoch, D., Michaud, A., Cohen, I., Humbert, A., Jaszczyszyn, Y., Chevreux, G., Del Maestro, L., Ait-Si-Ali, S., Arnaiz, O., Margueron, R., & Duharcourt, S. (2022). Paramecium Polycomb repressive complex 2 physically interacts with the small RNA-binding PIWI protein to repress transposable elements. Developmental Cell, 57(8), 1037-1052.e8.
Gnan, S., Matelot, M., Weiman, M., Arnaiz, O., Guérin, F., Sperling, L., Bétermier, M., Thermes, C., Chen, C.-L., & Duharcourt, S. (2022). GC content, but not nucleosome positioning, directly contributes to intron splicing efficiency in Paramecium. Genome Research, 32(4), 699–709.
Déléris, A., Berger, F., & Duharcourt, S. (2021). Role of Polycomb in the control of transposable elements. Trends in Genetics: TIG, 37(10), 882–889.
Sellis, D., Guérin, F., Arnaiz, O., Pett, W., Lerat, E., Boggetto, N., Krenek, S., Berendonk, T., Couloux, A., Aury, J.-M., Labadie, K., Malinsky, S., Bhullar, S., Meyer, E., Sperling, L., Duret, L., & Duharcourt, S. (2021). Massive colonization of protein-coding exons by selfish genetic elements in Paramecium germline genomes. PLoS Biology, 19(7), e3001309.
Hardy, A., Matelot, M., Touzeau, A., Klopp, C., Lopez-Roques, C., Duharcourt, S., & Defrance, M. (2021). DNAModAnnot: a R toolbox for DNA modification filtering and annotation. Bioinformatics (Oxford, England), btab032.
Grentzinger, T., Oberlin, S., Schott, G., Handler, D., Svozil, J., Barragan-Borrero, V., Humbert, A., Duharcourt, S., Brennecke, J., & Voinnet, O. (2020). A universal method for the rapid isolation of all known classes of functional silencing small RNAs. Nucleic Acids Research, 48(14), e79.
de Vanssay, A., Touzeau, A., Arnaiz, O., Frapporti, A., Phipps, J., & Duharcourt, S. (2020). The Paramecium histone chaperone Spt16-1 is required for Pgm endonuclease function in programmed genome rearrangements. PLoS Genetics, 16(7), e1008949.
Frapporti, A., Miró Pina, C., Arnaiz, O., Holoch, D., Kawaguchi, T., Humbert, A., Eleftheriou, E., Lombard, B., Loew, D., Sperling, L., Guitot, K., Margueron, R., & Duharcourt, S. (2019). The Polycomb protein Ezl1 mediates H3K9 and H3K27 methylation to repress transposable elements in Paramecium. Nature Communications, 10(1), 2710.
Arnaiz, O., Van Dijk, E., Bétermier, M., Lhuillier-Akakpo, M., de Vanssay, A., Duharcourt, S., Sallet, E., Gouzy, J., & Sperling, L. (2017). Improved methods and resources for paramecium genomics: transcription units, gene annotation and gene expression. BMC Genomics, 18(1), 483.
Guérin, F., Arnaiz, O., Boggetto, N., Denby Wilkes, C., Meyer, E., Sperling, L., & Duharcourt, S. (2017). Flow cytometry sorting of nuclei enables the first global characterization of Paramecium germline DNA and transposable elements. BMC Genomics, 18(1), 327.



Charmant, O., Gruchota, J., Arnaiz, O., Zangarelli, C., Betermier, M., Nowak, K., Legros, V., Chevreux, G., Nowak, J., & Duharcourt, S. (2023). The nuclear PIWI-interacting protein Gtsf1 controls the selective degradation of small RNAs in Paramecium. bioRxiv.
Miro-Pina, C., Arnaiz, O., Vanssay, A. de, Frapporti, A., Charmant, O., Humbert, A., Lhuillier-Akakpo, M., & Duharcourt, S. (2023). Non-catalytic function of PRC2 in the control of small RNA dynamics during programmed genome elimination in Paramecium. bioRxiv.



Balan, T., Lerner, L. K., Holoch, D., & Duharcourt, S. (2024). Small-RNA-guided histone modifications and somatic genome elimination in ciliates. WIREs RNA, 15(2), e1848.


Book chapter

Duharcourt, S., & Sperling, L. (2018). The Challenges of Genome-Wide Studies in a Unicellular Eukaryote With Two Nuclear Genomes. Methods in Enzymology, 612, 101–126.
  • Thomas Balan 2021 – fellowship from Université Paris Cité (ED BioSPC)
  • Olivia Charmant 2019 – 2023 – fellowships from Université Paris Cité, FRM
  • Caridad Miro-Pina 2016-2020- fellowships from Université Paris Cité and Fondation ARC
  • Amandine Touzeau 2014-2018 – fellowships from Université Paris Cité and Fondation ARC
  • Andrea Frapporti 2012-2016fellowships from Université Paris Cité and FRM
  • Maoussi Lhuillier-Akakpo 2010-2014 fellowships from Sorbonne Université and FRM

Raphaël Margueron (Institut Curie, Paris, France)

Olivier Arnaiz (I2BC, Gif-sur-Yvette, France)

Slimane Ait-Si-Ali (EDC, Université Paris Cité, France)

Eric Meyer (IBENS, Paris, France)

Laurent Duret (LBBE, Lyon, France)

Mireille Bétermier (I2BC, Gif-sur-Yvette, France)

Chunlong Chen (Institut Curie, Paris, France)

Hadi Quesneville (INRAE, Versailles, France)

Karine Labadie/ Jean-Marc Aury (Génoscope, Evry, France)

Thomas Berendonk (TU, Dresden, Germany)

Ewa Przybòs/Natalia Sawka (ISEA PAS, Krakow, Poland)

Alexey Potekhin (SPBU, St. Petersburg, Russia)

Matthieu Defrance (ULB, Brussels, Belgium)

Julita Gruchota/Jacek Nowak (IBB, Warsaw, Poland)

ANR LaMarque 2018-2022                                           




         LabEx Who Am I? 2021-2023


    FRM labelled team 2022-2025


04/07/2023 – Sandra Duharcourt, election as a member of the EMBO community

04/04/2022 – Sandra Duharcourt, CNRS Silver Medal