Epigenetic Regulation of Genome Organization
Themes and areas of research : Quantitative biology and modeling , Development and evolution , Cellular dynamics and signaling , Genome and chromosome dynamics , Models , Molecular and cellular pathologies
We study the epigenetic regulation of programmed genome rearrangements by non-coding RNAs, using the unicellular eukaryote Paramecium tetraurelia as a model organism. Our ultimate goal is to better understand the fundamental principles that govern chromosome structure and genetic stability in eukaryotes.
In this organism, the development of the somatic macronucleus from the germline micronucleus involves the precise excision of 50,000 short and unique internal eliminated sequences (IESs) from coding sequences and intergenic regions. Repeated sequences (transposon, minisatellites) are eliminated in an imprecise manner, often resulting in the fragmentation of germline chromosomes. Using genetics, genomics and cellular approaches, our research aims at deciphering the epigenetic mechanisms allowing the specific recognition of a very large number of different germline sequences that do not share any strictly conserved sequence motif.
In the recent years, our work has revealed the regulatory roles of two classes of ncRNAs in this process: (i) the piRNA-like scnRNAs, which are produced by the germline genome through a meiosis-specific RNAi pathway; and (ii) longer transcripts from the somatic genome. A natural genomic subtraction between these two populations of maternal non-coding RNAs would enable the selection of specific scnRNAs, which would ultimately target germline sequences for elimination, providing a RNA-based mechanism for the non–Mendelian inheritance of rearrangement patterns.
Current research themes:
- chromatin organization during development of the somatic macronucleus
- identification of germline centromere sequences
- mechanisms responsible for the inactivation of centromeres during development of the somatic macronucleus
The group is part of the Labex “Who am I?”
Selection of publications
Vanssay A, Touzeau A, Arnaiz O, Frapporti A, Phipps J, Duharcourt S.
The Paramecium histone chaperone Spt16-1 is required for Pgm endonuclease function in programmed genome rearrangements.
PLoS Genet. 2020 Jul 23 16(7)
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.
The Polycomb protein Ezl1 mediates H3K9 and H3K27 methylation to repress transposable elements in Paramecium.
Nat Commun. 2019 Jun 20;10(1)
Duharcourt S and Sperling L.
The Challenges of Genome-Wide Studies in a Unicellular Eukaryote With Two Nuclear Genomes.
Methods Enzymol. 2018;612:101-126. Epub 2018 Aug
Guérin F, Arnaiz O, Boggetto N, Denby Wilkes C, Meyer E, Sperling L and Duharcourt S.
Flow cytometry sorting of nuclei enables the first global characterization of Paramecium germline DNA and transposable elements.
BMC Genomics. 2017 Apr 26;18(1):327.
Lhuillier-Akakpo M, Guérin F, Frapporti A and Duharcourt S.
DNA deletion as a mechanism for developmentally programmed centromere loss.
Nucleic Acids Res. 2015 Oct 25.
Lhuillier-Akakpo M*, Frapporti A*, Denby Wilkes C, Matelot M, Vervoort M, Sperling L, Duharcourt S.
Local effect of Enhancer of Zeste-like reveals cooperation of epigenetic and cis-acting determinants for zygotic genome rearrangements.
PLoS Genet. 2014 Sep 25;10(9):e1004665.eCollection 2014 Sep.
Singh DP, Saudemont B, Guglielmi G, Arnaiz O, Goût JF, Prajer M, Potekhin A, Przybòs E, Aubusson-Fleury A, Bhullar S, Bouhouche K, Lhuillier-Akakpo M, Tanty V, Blugeon C, Alberti A, Labadie K, Aury JM, Sperling L, Duharcourt S, Meyer E.
Genome-defence small RNAs exapted for epigenetic mating-type inheritance.
Nature. 2014 May 22;509(7501):447-52. Epub 2014 May 7.
Arnaiz O, Mathy N, Baudry C, Malinsky S, Aury JM, Denby Wilkes C, Garnier O, Labadie K, Lauderdale BE, Le Mouël A, Marmignon A, Nowacki M, Poulain J, Prajer M, Wincker P, Meyer E, Duharcourt S, Duret L, Bétermier M, Sperling L.
The Paramecium Germline Genome Provides a Niche for Intragenic Parasitic DNA: Evolutionary Dynamics of Internal Eliminated Sequences.
PLoS Genet. 2012 Oct;8(10):e1002984.