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Dr Jérome Déjardin, IGH Montpellier – The control of transposable elements by chromatin
11 décembre 2019 @ 11:00 - 12:00
Metastable epialleles are alleles variably expressed in genetically identical individuals. The nearby insertion of an endogenous retrovirus (ERV), particularly of the Intracisternal A Particle (IAP) class, is a major feature of mouse epialleles. Some IAP insertions are variably methylated between individuals and can influence neighboring gene expression providing « epigenetic » inter-individual differences. How metastable expression patterns are established and maintained at transposons and epialleles in mammals remain unknown. With the goal to understand these biological phenomena, we developed a proteomic screen –a locus specific chromatin purification- to analyse the composition of IAP chromatin in pluripotent stem cells, in differentiated cells and in relevant mutant backgrounds. Our proteomics revealed changes in IAP chromatin composition in different cell types, notably with the complete loss of KZFPs/KAP1/SETDB1 recruitment, while DNMT1, MeCP2 and UHRF1 remain bound in differentiated cells. Interestingly, our screens also identified transcription factors and factors implicated in nuclear organisation, supporting the idea that some IAPs have the potential to work as regulatory sequences and to impact on variable gene expression. Finally, isolated IAP chromatin interactome support that IAPs contact specific genomic regions like microsatellites known to be prone to instabilities. Our latest data and hypothesis on this project will be presented.