Repeated DNA sequences represent an important part of eukaryotic genomes. Satellite DNA sequences are localized at the centromeric regions of chromosomes while transposable elements are dispersed along chromosome arms. The purpose of our team is to characterize the diversity of this genetic material, its evolutionary mechanisms as well as their impact on cellular physiology. Towards this aim, we implement a multidisciplinary approach based on molecular and cellular biology, imaging, bioinformatics and data analysis. Our long term goal is to understand how those sequences contribute to the regulation of genomes activity and stability and what constraints will affect their evolution. There are three major aspects in our work :

• Diversity and evolutionary history of alpha satellite DNA in primates
• Epigenetic modifications of repeated DNA
• Repeated DNA and 3D genome organization.

Responsables de l'équipe:

• Escudé Christophe, CR CNRS                    
• Mozziconacci Julien, PR MNHN

Membres de l'équipe:

• Lopes Judith, CR INSERM                              
• Ponger Loic, MCF MNHN
• Marques Xavier, IE MNHN
• Pichon Julien, Doctorant
• Westbrook Alex, Doctorant
• Christophe Maxime, Doctorant
• Drayton- Libotte Bernadette, IE INSERM

Former members:

• Goué Anaïs, CDD IE MNHN 
• Manel Ait El Hadj, M2 Paris-Saclay
• Boutorine Alexandre, PR MNHN               
• Strauss François, DR CNRS                    
• Cacheux Lauriane, Doctorante      
• Decombe Sheldon, Doctorant       
• Kolar-Znika Lorena, Doctorante
• Nozeret Karine, Doctorante      
• Ollion Jean, Doctorant   
• Haschka Thomas, ATER MNHN
• El Asri Merwan, M2
• Goué Anaïs ,M2        
• Marnier Guilhem, M2
• Van der Meersche Yann, M2
• Gueguen Louis-Maël, M1        
• Haddad Noëlle, M1        

​Diversity and evolutionary history of alpha satellite DNA in primates

We have undertaken the characterization of alpha satellite DNA sequences in several Old World monkey species. This work, which relies on computational approaches and cytogenetics, sheds a new light on the mechanisms that sustain the peculiar evolution of satellite DNA but also helps in understanding the evolution of species. It is made possible through a collection of cryopreserved cells available at the MNHN.

Classification of alpha satellite DNA from cercopithecus pogonias

Credits

©Loic.Ponger

​Epigenetic modifications of repeated DNA

We implement strategies for epigenetic engineering of repeated DNA, that rely upon specific targeting of chromatin modifying enzymes in human and mouse cells. This work enables, for example, to understand the role of the H3K9me3 chromatin mark, that is highly abundant in pericentromeric regions, on genome stability and organization.

Tale mediated targeting of a histone demethylase to pericentromeric heterochromatin in mouse cells

Credits

©Judith_Lopes

​Repeated DNA and 3D genome organization.

We are interested in understanding how various types of repeated DNA participate to the 3D folding of genomes in cell nuclei. Towards this aim, we have developped an image analysis tool specifically devoted to the nuclear organization of genomes as well as quantitative approaches for analysis of HiC data. This work will characterize the dynamics of chromatin compartments as well as their contribution to gene regulation mechanisms.

Experimental approaches for studying the 3D organization of genomes

Credits

©C.Escudé

Networks

Institut Universtitaire de France 

GDR ADN 

​Selected publications:

Ollion, J., Loll, F., Cochennec, J., Boudier, T. and Escudé, C. Proliferation-dependent positioning of individual centromeres in the interphase nucleus of human lymphoblastoid cell lines. Molecular Biology of the Cell (2015) 26, 2550-2560.

Cacheux, L., Ponger, L., Gerbault-Seureau, M., Loll, F., Gey, D., Richard, F.A. and Escudé, C. The Targeted Sequencing of Alpha Satellite DNA in Cercopithecus pogonias Provides New Insight into the Diversity and Dynamics of Centromeric Repeats in Old World monkeys Genome Biol. Evol. (2018) 10, 1837-1851.

Haschka, T., Ponger, L., Escudé, C. and Mozziconacci, J. (2021) MNHN-Tree-Tools: A toolbox for tree inference using multi-scale clustering of a set of sequences. Bioinformatics btab430

Decombe, S., Loll, F., Caccianini, L., Affannoukoué, K., Izeddin, I., Mozziconacci, J., Escudé, C. and Lopes, J. (2021) Epigenetic rewriting at centromeric DNA repeats leads to increased chromatin accessibility and chromosomal instability bioRxiv 2021.02.22.432244 

A Cournac, R Koszul, J Mozziconacci (2016) The 3D folding of metazoan genomes correlates with the association of similar repetitive elements Nucleic acids research 44, 245-255