Chromatin and epigenetic regulation

The main research activity of our group is to study the role of histone variants and their deposition machineries in the epigenetic control of human genome activity at the genome- wide level. Among the various epigenetic memory mechanisms, the local replacement of canonical histones within the nucleosome by variant histones has the potential to affect considerably the activity of the corresponding genomic regions. Indeed, nucleosomes bearing histone variants have distinct structures and functional activities in vitro and some histone variants are incorporated at specific genomic locations. Our laboratory is focusing on the role of histone variants in gene regulation and genome integrity. We have recently implicated macroH2A in PARP-1 enzymatic activity and transcription regulation (Ouararhni et al., 2006), and discovered a new link between histone variants, transcription factors and non- coding RNA (unpublished results). This association with transcription factors and non-coding RNA is novel and will certainly help us to understand how chromatin domains are established and how epigenetic information is stored and transmitted to daughter cells. Alteration of these epigenetic marks is associated with developmental disorders and cancer.