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Le laboratoire étudie l’implication des
modifications chromatiniennes et des enzymes qui les établissent, dans la
prolifération cellulaire contrôlée des cellules de mammifères. Ces
enzymes sont susceptibles d’affecter à long terme et parfois de manière transmissible
(information épigénétique) l’état fonctionnel de la chromatine. Ainsi,
elles interviennent en particulier dans la mise en place ou la répression
de programmes génétiques particuliers.
L’équipe s’intéresse notamment au contrôle
des gènes activés au cours du cycle cellulaire (gènes cibles de E2F) et
au programme génétique de la différenciation terminale musculaire.
Un autre pan de nos travaux vise à comprendre
les mécanismes moléculaires par lesquels le complexe Tip60 (qui contient
aussi l’ATPase p400) participe à la réponse transcriptionnelle aux
dommages à l’ADN et à l’induction de l’apoptose.
Les enzymes de modification de la chromatine
interviennent aussi dans le maintien du patrimoine génétique au cours du cycle
cellulaire. Notre équipe étudie ainsi le rôle de ces enzymes dans la
réparation de l’ADN, notamment après cassures double brins. Nous nous
focalisons notamment sur le rôle du complexe Tip60 dans cette réparation,
mais nous avons également développé un système permettant l’étude des
déterminants chromatiniens de la réparation des cassures double-brin à
l’échelle du génome.
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The group studies the
involvement of chromatin modifications and the enzymes which regulate
them in the controlled proliferation of mammalian cells. These enzymes
can affect for long and sometimes in a heritable manner (epigenetic
information) the functional status of chromatin. Thus, they participate
in the regulation of specific genetic programs.
More specifically, the
group investigates the transcriptional regulation of E2F-regulated genes,
which represent genes associated with cell proliferation, as well as
genes activated during muscle terminal differentiation.
Another topic studied in
the lab is about the Tip60 complex (a multimolecular complex composed of
proteins associated with the Tip60 histone acetyl transferase, such the
ATPase p400) and its role in cell proliferation control, in particular in
response to DNA damage. Its relationship with human cancer is also investigated.
The chromatin modifying
enzymes also participate in genomic stability during the mammalian cell
cycle. We are studying the role of these enzymes in the repair of DNA
damages, such as DNA double strand breaks (DSBs). We focus in particular
on the role of the Tip60 complex in the repair of DNA DSBs. Moreover, we
developed a new system allowing the study of the chromatin determinants
of DNA DSB repair at a chromosomal level.
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Publications :
Verrier L,
Vandromme M, Trouche D. (2011) Histone demethylases in chromatin
cross-talks. Biol Cell. 103(8):381-401. Review.
Verrier L,
Escaffit F, Chailleux C, Trouche D, Vandromme M. (2011) A new isoform of
the histone demethylase JMJD2A/KDM4A is required for skeletal muscle
differentiation. PLoS Genet. 7(6):e1001390.
*Mattera, L., *Courilleau, C. (*co-first
authors), Legube, G., Ueda, T., Fukunaga, R., Chevillard-Briet, M.,
§Canitrot, Y., §Escaffit, F. (§ equal contribution), Trouche, D. (2010)
The E1A-associated p400 protein modulates cell fate decision by the regulation
of ROS homeostasis. PLoS
Genet. 6(6):e1000983. Abstract.
*Iacovoni JS, *Caron P (*co-first authors)),
Lassadi I, Nicolas E, Massip L, #Trouche D, #Legube G (#co-last
authors).(2010) High-resolution profiling of gammaH2AX around DNA double
strand breaks in the mammalian genome. EMBO J. 29(8):1446-57. Abstract.
Chailleux C, Tyteca S, Papin C, Boudsocq
F, Puget N, Courilleau C, Grigoriev M, Canitrot Y, Trouche D. (2010)
Physical interaction between the
histone acetyl transferase Tip60 and the DNA double-strand breaks sensor
MRN complex. Biochem J. 426(3):365-71. Abstract.
Pillaire MJ, Selves J, Gordien K, Gouraud PA,
Gentil C, Danjoux M, Do C, Negre V, Bieth A, Guimbaud R, Trouche D,
Pasero P, Méchali M, Hoffmann JS, Cazaux C. (2010) A ’DNA replication’
signature of progression and negative outcome in colorectal cancer.
Oncogene. 29(6):876-87. Abstract.
*Mattera, L., *Escaffit, F. (*co-first
authors), Pillaire, M.-J., Selves, J., Tyteca, S., Hoffmann, J.-S.,
Gourraud, P.-A., §Chevillard-Briet, M., §Cazaux, C. (§ equal
contribution), Trouche, D. (2009) The p400/Tip60 ratio is critical for
colorectal cancer cells proliferation through DNA damage response
pathways. Oncogene. 28(12):1506-17. Abstract.
*Vandromme, M., *Chailleux, C. (*co-first
authors), Escaffit, F., Trouche, D. (2008) Binding of the Retinoblastoma
protein is not the determinant for stable repression of some
E2F-regulated promoters in muscle cells. Mol. Cancer Res. 6 : 418-425. Abstract.
Escaffit, F., Vaute, O., Chevillard-Briet,
M., Ségui, B., Takami, Y., Nakayama, T. and Trouche, D. (2007) Cleavage
and cytoplasmic relocalisation of histone deacetylase 3 is important for
apoptosis progression. Mol. Cell. Biol. 27 :
554-567. Abstract.
Tyteca, S., Legube, G., Trouche, D. (2006) To
die or not to die : a HAT trick. Mol Cell 24 : 807-808. Abstract.
Tyteca, S.,
Vandromme, M., Legube, G., Chevillard-Briet, M., Trouche, D. (2006)
Independent roles of Tip60 and p400 in DNA damage-induced apoptosis. EMBO
J., 25: 1680-1689. Abstract.
Selected by EMBO J
editors as one of the four best papers published by EMBO J during the
first half of 2006 (EMBO encounters 6, summer 2006).
*Daury, L., *Chailleux, C. (*co-first
authors), Trouche, D. (2006) Deposition of histone H3.3 on E2F responsive
genes is linked to transcription. EMBO R. 7: 66-71. Abstract.
Nicolas, E., Daury, L., Trouche, D. (2005)
Regulation of E2F-responsive genes through histone modifications. In Rb
and Tumoriginesis, M Fanciulli (Ed), Landes Biosciences. Abstract.
Régnier, V. (corresponding author),
Vagnarelli, P., Fukagawa, T., Zerjal, T., Burns, E., Trouche, D.,
Earnshaw, W., Brown, W. R. (2005) CENP-A is required for accurate
chromosome segregation and sustained kinetochore association of BubR1. Mol.
Cell. Biol. 25: 3967-3981. Abstract.
Pour
plus d’information, visitez le site web de l’équipe : www.trouche.fr
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