An ambitious EC-funded research initiative on epigenetics advancing towards systems biology

DNA replication starts at 30 000-50 000 DNA replication origins along human chromosomes. We wish to decipher their genetic and epigenetic nature and, and unravel their function in the cell cycle. We also aim at dissecting the molecular mechanisms involved in initiation of DNA replication. Using genome-wide analyses of mouse and human pluripotent stem cells and differentiating cells, we characterized several new features of replication origins, including an Origin G-rich Repeated Element (OGRE) that can form G-quadruplexes. We also found that replicons contain several flexible origins, which can be used differently from cell to cell. We proposed that replication origins define a new barcode on chromosomes that is characteristic of the cell identity. We are also identifying new replication proteins. We have characterized Cdt1, MCM8, MCM9 and MCM-BP. Recently, we found that MCM8 and MCM9 form a new complex involved in the control of recombination, DNA repair and animal fertility. Their deregulation leads to cancers.

List the PhDs and Postdocs involved in research on EpiGeneSys projects; include their titles:

• Marcel Méchali Research Director, CNRS
• Christelle Cayrou Research Scientist, CNRS
• James Hutchins. Research Scientist, CNRS
• Malik Lutzmann Research Scientist, CNRS
• Philippe Coulombe Post-doc
• Olivier Ganier Post-doc
• Hanane Agherbi Post-doc (leaving 2013)
• Michailis Fragkos Post-doc (leaving 2013)
• Marta Rodriguez PhD Student
• Fabien Velilla PhD Student