Epigenetic Regulation of Genome Organization

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.

Nuclear dualism in Paramecium. Each cell contains 2 types of nuclei : the diploid and transcriptionally silent micronuclei (mics) that only serve germline functions, and a polyploid somatic macronucleus (MAC) that is responsible for gene expression. Image of a Paramecium cell: localization of a GFP-tagged mic-specific protein by confocal microscopy in vegetative cells. GFP is shown in red, whereas DNA is stained with DAPI (blue). Copyright CNRS/ ENS/ IJM/ S. Duharcourt.

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
  
  

Selection of publications

Coyne RS*, Lhuillier-Akakpo M*, Duharcourt S. (* equal contribution)
RNA-guided DNA rearrangements in ciliates: Is the best genome defense a good offense?
Biol Cell. 2012. 104, 1–17.
Abstract

Beisson J, Bétermier M, Bré M-H, Cohen J, Duharcourt S, Duret L, Kung C, Malinsky S, Meyer E, Preer JR Jr, Sperling L.
Paramecium tetraurelia: The Renaissance of an Early Unicellular Model.
Cold Spring Harb Protoc. 2010.
Abstract

Duharcourt S, G Lepère & E. Meyer.
Developmental genome rearrangements in ciliates: a natural genomic subtraction mediated by non-coding transcripts.
Trends Genet. 2009. 25(8):344-50.
Abstract

Lepère G, M. Nowacki, V. Serrano, J.-F. Gout, S. Duharcourt & E. Meyer.
Silencing-associated and meiosis-specific small RNA pathways in Paramecium tetraurelia.
Nucleic Acids Res. 2009. 37: 903-915.
Abstract

Lepère G, Bétermier M, Meyer E & S. Duharcourt.
Maternal noncoding transcripts antagonize the targeting of DNA elimination by scanRNAs in Paramecium tetraurelia.
Genes Dev. 2008. 22 :1501-1512.
Abstract

Last modified 05/14/2012

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