Regulation of chromatin modifiers by metabolites of the Krebs cycle

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In the nucleus of eukaryotic cells, the genome is tightly packed into chromatin, a complex arrangement of protein and DNA. The chromatin structure governs the establishment and maintenance of gene expression patterns, and is therefore determinant in several critical outcomes at the cellular levels, such as differentiation and genome stability. Interestingly, recent evidences have demonstrated that numerous chromatin modifiers are regulated by metabolites issued from mitochondria, a specialized energy-producing organelle in eukaryotic cells. We therefore anticipate that metabolism alterations results into chromatin modifications and gene expression changes. Our research aims to document extensively the molecular outcomes of metabolite unbalance at the level of chromatin, and to uncover metabolic-responsive gene pathways. The novelty of our research resides into an unbiased approach and extensive analysis of all possible modifications induced by metabolite alterations. We will make use of two complementary biological models, human cells and C.elegans, a classical model for in vivo studies. Ultimately we will contribute to our knowledge on a fascinating metabolism-epigenetics crosstalk.