Genetic Instabilities and Control by the Host genome
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Institute of Genetics Reproduction and Development (iGReD), CNRS UMR6293, inserm U1103, Université Clermont Auvergne
Faculté de médecine – CRBC
28, Place Henri Dunant
63000 Clermont-Ferrand
France
Scientific Interest
Eukaryotic genomes are mainly composed of repeated sequences including transposable elements (TEs), highly mutagenic mobile DNA sequences which constitute a serious threat for the genome integrity. TEs reside in the genome of all species and represent half of the human genome. A tight control of TE expression is essential to avoid their mobilization and the emergence of pathologies, while taking advantage of their evolutionary skills. A first level of TE control is necessary in the germline cells, since their genetic information will be transmitted to the progeny. Ten years after the discovery of the first small non-coding RNAs, a new class of small RNAs, piRNAs, was discovered in the germline of all metazoans including human. These piRNAs appeared to be key regulators of TE expression and a fine regulation of their expression is required to avoid the appearance of pathologies. Despite the evolutionary distance which separates Drosophila from humans, a strong conservation of the piRNA pathway has been demonstrated. Drosophila is therefore an excellent model for studying this pathway. The millions of piRNAs produced by germ cells originate from particular genomic loci called piRNA clusters. These clusters are composed of a multitude of TEs, and represent the repertoire of TEs that the cell must repress to maintain the genome stability. However, following a reactivation of TEs in somatic tissue adjacent to germ cells, some TEs are able to infect and invade the germline genome as a virus would do. Our projects aim to understand the transcriptional regulation of piRNA clusters during development and how TE repression takes place in the organisms. Combined confocal and electron microscopy, genetics, genomics, genome editing, sequencing and bioinformatic approaches are used to conduct these projects. The original approaches that we develop will provide essential answers on the role of small non-coding RNAs in maintaining genome integrity.
Eukaryotic genomes are mainly composed of repeated sequences including transposable elements (TEs), highly mutagenic mobile DNA sequences which constitute a serious threat for the genome integrity. TEs reside in the genome of all species and represent half of the human genome. A tight control of TE expression is essential to avoid their mobilization and the emergence of pathologies, while taking advantage of their evolutionary skills. A first level of TE control is necessary in the germline cells, since their genetic information will be transmitted to the progeny. Ten years after the discovery of the first small non-coding RNAs, a new class of small RNAs, piRNAs, was discovered in the germline of all metazoans including human. These piRNAs appeared to be key regulators of TE expression and a fine regulation of their expression is required to avoid the appearance of pathologies. Despite the evolutionary distance which separates Drosophila from humans, a strong conservation of the piRNA pathway has been demonstrated. Drosophila is therefore an excellent model for studying this pathway. The millions of piRNAs produced by germ cells originate from particular genomic loci called piRNA clusters. These clusters are composed of a multitude of TEs, and represent the repertoire of TEs that the cell must repress to maintain the genome stability. However, following a reactivation of TEs in somatic tissue adjacent to germ cells, some TEs are able to infect and invade the germline genome as a virus would do. Our projects aim to understand the transcriptional regulation of piRNA clusters during development and how TE repression takes place in the organisms. Combined confocal and electron microscopy, genetics, genomics, genome editing, sequencing and bioinformatic approaches are used to conduct these projects. The original approaches that we develop will provide essential answers on the role of small non-coding RNAs in maintaining genome integrity.
Thematic