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Laboratory | Epigenetics
Team LeaderMatthieu GERARDmatthieu.email@example.com
This Research Team is part of the I2BC
This three cell type differ in their state of pluripotency, differentiation and proliferation: embryonic stem (ES) cells, neuronal precursor cells and post-mitotic neurons. For this project, we have generated a collection of mouse ES cell lines, each expressing a tagged version of a remodeler. We are using genome-wide approaches including ChIP-seq (chromatin immunoprecipitation sequencing; Figure 1) and loss-of-function coupled to RNA-seq transcriptome analysis, to characterize the genome-wide distribution of remodelers and study their contribution to the regulation of gene expression. Our recent investigations revealed that remodelers have not only key functions in the control of transcriptional programs, but are also essential for the maintenance of the ES cell phenotype. We are currently investigating their functional specificities in neuronal precursor cells and neurons.
We are testing the hypothesis that neuronal aging may be associated with progressive alterations of the nucleosomal barrier, resulting in changes in brain transcriptional programs.
We are currently studying two remodelers that are the major binding partners of histone deacetylase 2 (HDAC2; Figures 1 and 2) in the brain. It has recently been shown that HDAC2 is overexpressed in Alzheimer's disease patients, resulting in repression of genes required for memory formation and synaptic plasticity, and in cognitive impairment (Gräff et al. 2012; PMID: 22388814). Our aim is to understand how chromatin remodeling and histone deacetylation contribute to dysregulation of genome expression at different stages of the pathology, and to identify novel pathways that could be targeted for early treatment of learning and memory deficits and prevention of cognitive decline.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.