.

Epigenetic Regulation of Genome Organization

Sandra DUHARCOURT

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)ijm.fr      @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.

Group Leader:

Sandra DUHARCOURT
Tél : +33 (0)157278009
email : sandra.duharcourt (at) ijm.fr

 

Members :

Thomas BALAN, PhD Student

Mathieu BRUGGEMAN, postdoc

Olivia CHARMANT, PhD Student

Caridad MIRO PINA, Biological Engineer

https://www.insb.cnrs.fr/fr/cnrsinfo/faire-taire-les-elements-genetiques-mobiles-dans-le-genome

https://www.cell.com/developmental-cell/issue?pii=S1534-5807(21)X0009-3

https://www.insb.cnrs.fr/fr/cnrsinfo/la-composition-nucleotidique-des-introns-contribue-directement-lefficacite-de-leur

https://genome.cshlp.org/content/32/4.cover-expansion

https://insb.cnrs.fr/fr/cnrsinfo/invasion-massive-delements-genetiques-egoistes-dans-les-genes-de-paramecie

Primer: Feng Y, Landweber LF (2021) Transposon debris in ciliate genomes. PLoS Biol 19(8): e3001354. https://doi.org/10.1371/journal.pbio.3001354

http://www.insb.cnrs.fr/fr/cnrsinfo/une-enzyme-pas-comme-les-autres-fait-taire-les-sequences-repetees-du-genome

Une enzyme pas comme les autres fait taire les séquences répétées du génome.pdf

https://www.insb.cnrs.fr/fr/cnrsinfo/faire-taire-les-elements-genetiques-mobiles-dans-le-genome

https://www.cell.com/developmental-cell/issue?pii=S1534-5807(21)X0009-3

https://www.insb.cnrs.fr/fr/cnrsinfo/la-composition-nucleotidique-des-introns-contribue-directement-lefficacite-de-leur

https://genome.cshlp.org/content/32/4.cover-expansion

https://insb.cnrs.fr/fr/cnrsinfo/invasion-massive-delements-genetiques-egoistes-dans-les-genes-de-paramecie

Primer: Feng Y, Landweber LF (2021) Transposon debris in ciliate genomes. PLoS Biol 19(8): e3001354. https://doi.org/10.1371/journal.pbio.3001354

http://www.insb.cnrs.fr/fr/cnrsinfo/une-enzyme-pas-comme-les-autres-fait-taire-les-sequences-repetees-du-genome

Une enzyme pas comme les autres fait taire les séquences répétées du génome.pdf

 

  • Thomas Balan 2021 – fellowship from Université Paris Cité (ED BioSPC)
  • Olivia Charmant 2019 – fellowship from Université Paris Cité
  • 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                                           

ANR POLYCHROME 2019-2023

 

         LabEx Who Am I? 2021-2023

 

    FRM labelled team 2022-2025

 

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

 

An Assistant Professor position is open at the Université Paris Cité and the Institut Jacques Monod (équipe Duharcourt) on the mechanisms and regulation of genome dynamics in paramecium.

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