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

The general aim of the lab is to give insights into the function of chromatin during DNA Double Strand Break (DSB) repair. Indeed whereas DSB repair mechanisms are quite well characterized and subjected to extensive studies, in contrast, the contribution of chromatin in these processes still remains poorly understood.

We have developed a new system, based on a restriction enzyme fused to the ligand-binding domain of oestrogen receptor (AsiSI-ER), in order to generate multiples (~150) sequence-specific DSBs on the human genome (Massip et al, 2010). Since it generates unambiguously positioned DSBs, one can use ChIP-chip/seq to draw high resolution profiles of DSB-induced chromatin modification and DNA repair complexes around breaks. Using this system, we reported the first high resolution maps of DSB-induced chromatin modifications (gH2AX and cohesin de novo targeting) by ChIP-chip (Caron et al, 2012; Iacovoni et al, 2010). We are now trying to describe more thoroughly the chromatin landscape induced around DSBs, to understand how chromatin contributes to recruit the adequate repair factors at site of DSBs and to investigate how this DSB-specific chromatin landscape is removed to recover the original epigenetic modifications and maintain cell fate.

Lab members involved:

• Bugler Beatrix, Staff scientist, CNRS
• Guillou Emmanuelle, PostDoc
• Clouaire Thomas, PostDoc
• Caron Pierre, PhD
• Aymard Francois, PhD
• Choudjaye Jonathan, PhD
• Daburon Virginie, Technician
• Arrigenboa Marion, Engineer in Biostatistics