Basic Research Team 2 « Retrotransposons and genome plasticity »
Dr Gaël CRISTOFARI, CR1 INSERM, Team Leader
Presentation
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The abundance of transposable elements in the human genome was one of the most surprising and disconcerting discoveries of genomics.
More than 40 % of our DNA is made of mobile genetic elements, also called “jumping genes” (see Fig.1).
Human retrotransposons (LINE-1 and Alu) and human endogenous retroviruses (HERVs) are highly repetitive and dispersed sequences, which account for half of our DNA.
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They can proliferate through an RNA-mediated copy-and-paste mechanism, called retrotransposition (see Fig. 2).
This process can drive profound genome rearrangements. It plays a central role in the plasticity of mammalian genomes and in human genome diversity. Although generally silent, retrotransposons are expressed in germ cells, in the early embryo, and in embryonic stem cells, which occasionally results in genetic diseases.
They are also massively re-expressed in the large majority of cancers. However the importance and consequences of retrotransposition on human health have been poorly studied, mostly due to difficulties in tracking new insertion events in clinical samples. Indeed it is extremely difficult to detect a new copy in a new locus among the hundreds of thousands copies inherited from our parents.
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Research Project
The questions we wish to address in our group are the following :
(i) What cellular pathways control retrotransposon copy number ? We combine functional genomics and proteomics approaches to identify positive and negative regulators of retrotransposition in humans.
(ii) What are the molecular mechanisms of retrotransposons replication ? We develop in vitro assays containing the complete retrotransposition machinery to study step-by-step this mutagenic process.
(iii) How retrotransposons participate in the policenormal and pathological remodeling of the human genome ? To this purpose we are currently developing innovative approaches using next-generation sequencing technologies and bioinformatics to track retrotransposition events in clinical samples, especially in tumor samples.
Understanding how the activity of retrotransposons is controlled will impact our knowledge of the mechanisms that lead to new genetic diseases or to cancer progression. Since mobile genetic elements are becoming important tools in insertional mutagenesis or gene-transfer technologies in mammals, our work should also help to improve and widen the use of retrotransposons in mammalian functional genomics or gene-therapy.
Research Team
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Back row (left to right) : Ashfaq, Clement, Jorge, Claude, Sebastien.
Front row (left to right) : Pilvi, Serdar, Gael, Monika |
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Last
name | First
Name | Title | | Phone* | Email |
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| Principal Investigator |
| CRISTOFARI |
Gael |
PhD |
INSERM |
70 87 |
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| Research Assistants |
| PHILIPPE |
Claude |
PhD |
CNRS |
70 19 |
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| LAGHA |
Nadira |
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70 19 |
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| Postdocs |
| VERA OTAROLA |
Jorge |
PhD |
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70 19 |
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| GARCIA-PIZARRO |
Javier |
PhD |
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70 17 |
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| KASAKYAN |
Serdar |
PhD |
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70 17 |
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| PhD Students |
| MONOT |
Clément |
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ARC fellow |
70 17 |
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| VIOLLET |
Sébastien |
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70 19 |
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| MIR |
Ashfaq |
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| Master Students |
| MONTANDON |
Margo |
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70 17 |
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| ANTONAZZO |
Giulia |
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xx xx |
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| TEL.: * +33 (0)4 93 37 XX XX |
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Publications
Monot C*, Kuciak M*, Viollet S, Mir AA, Gabus C, Darlix JL, Cristofari G. (2013) The specificity and flexibility of L1 reverse transcription priming at imperfect T-Tracts. PLoS Genet. In Press. (* co-first authors)
Goic B, Vodovar N, Mondotte JA, Monot C, Frangeul L, Blanc H, Gausson V, Vera-Otarola J, Cristofari G, Saleh MC. (2013) RNA-mediated interference and reverse transcription control the persistence of RNA viruses in the insect model Drosophila. Nat Immunol. 14(4):396-403. [Abstract] [Full Text] [PDF] [PubMed]
Sauerwald A, Sandin S, Cristofari G, Scheres SH, Lingner J, Rhodes D. (2013) Structure of active dimeric human telomerase. Nat Struct Mol Biol. 20(4):454-60. [Abstract] [Full Text] [PDF] [PubMed]
Ainouche A, Bétermier M, Chandler M, Cordaux R, Cristofari G, Deragon JM, Lesage P, Panaud O, Quesneville H, Vaury C, Vieira C, Vitte C. (2012) International Congress on Transposable Elements (ICTE) 2012 in Saint Malo and the sea of TE stories. Mobile DNA. 3(1):17. [Abstract] [Full Text] [PDF] [PubMed]
Vidale P, Magnani E, Nergadze SG, Santagostino M, Cristofari G, Smirnova A, Mondello C, Giulotto E. (2012) The catalytic and the RNA subunits of human telomerase are required to immortalize equid primary fibroblasts. Chromosoma. 121(5):475-88. [Abstract] [Full Text] [PDF] [PubMed]
Chaurasiya KR, Geertsema H, Cristofari G, Darlix JL, Williams MC. (2012) A single zinc finger optimizes the DNA interactions of the nucleocapsid protein of the yeast retrotransposon Ty3. Nucleic Acids Res. 40:751-60. [Abstract] [Full Text] [PDF] [PubMed]
Abreu E, Aritonovska E, Reichenbach P, Cristofari G, Culp B, Terns RM, Lingner J, Terns MP. (2010) TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo. Mol Cell Biol. 30:2971-82 [Abstract] [Full Text] [PDF] [PubMed]
Kurth I, Cristofari G, Lingner J. (2008) An affinity oligonucleotide displacement strategy to purify ribonucleoprotein complexes applied to human telomerase. Methods Mol Biol. 488:9-22. [Abstract] [PubMed]
De Cian A, Cristofari G, Reichenbach P, Delemos E, Monchaud D, Teulade-Fichou MP, Shin-ya K, Lacroix L, Lingner J, & Mergny JL. (2007) Re-evaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action. Proc. Natl Acad. Sci. USA. 104(44):17347-17352. [Abstract] [Full Text] [PDF] [PubMed]
Cristofari G, Reichenbach P, Regamey PO, Banfi D, Chambon M, Turcatti G, Lingner J. (2007) Low- to high-throughput analysis of telomerase modulators with Telospot. Nat. Methods. 4(10):851-853. [Abstract] [PubMed]
Cristofari G, Adolf E, Reichenbach P, Sikora K, Terns RM, Terns MP, Lingner J. (2007) Human telomerase RNA accumulation in Cajal bodies facilitates telomerase recruitment to telomeres and telomere elongation. Mol. Cell. 27(6):882-889. [Abstract] [PubMed]
Cristofari G, Lingner J. (2006) Telomere length homeostasis requires that telomerase levels are limiting. EMBO J. 25(3):565-74. [Abstract] [Full Text] [PDF] [PubMed]
Cristofari G, Bampi C, Wilhelm M, Wilhelm FX, Darlix JL. (2002) A 5'-3' long-range interaction in Ty1 RNA controls its reverse transcription and retrotransposition. EMBO J. 21(16):4368-79. [Full Text] [PDF] [PubMed]
Cristofari G, Darlix JL. (2002) The ubiquitous nature of RNA chaperone proteins. Prog Nucleic Acid Res. Mol. Biol. 72:223-68. [Abstract] [PDF] [PubMed]
Open positions
If you are interested in joining the Cristofari lab, for a postdoc, a PhD work or an internship, don't hesitate to directly contact Gael Cristofari at:
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