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> Stages de M2 > Liste des stages proposés pour l année 2018-2019 > Role of pluripotency factors in the maintenance of genomic imprinting

Role of pluripotency factors in the maintenance of genomic imprinting

proposé par Robert FEIL, , laboratoire ‘Genomic Imprinting and Development’, IGMM, Montpellier

Projet de stage : (une vingtaine de lignes maximum)

The proposed project concerns the mono-allelic expression (from one of the two copies only) of ‘imprinted genes’, a group of essential genes involved in development, metabolism and behavior, and whose expression depends entirely on whether they are inherited from mother or from father. The underlying epigenetic mechanisms -called ‘genomic imprinting’- is essential for development and involves parentally inherited DNA methylation marks at regulatory sequences. The faithful maintenance of imprinted gene expression in ESCs and in the early embryo has been linked to whether or not embryonic cells maintain their pluripotency. We hypothesize that this is because pluripotency-associated transcription factors are recruited to imprinted gene loci, and protect against aberrant gains of DNA methylation. The training project focuses on pluripotency factors that bind to specific disease-associated imprinted gene loci. We hypothesize that that this new insight is relevant to human imprinting diseases, which are often caused by aberrant gains of DNA methylation during the preimplantation stage of development. The aim of the project is to explore in mouse ESCs the importance of pluripotency factor binding to differentially methylated regions (DMRs) at imprinted gene loci. One or two disease-associated imprinted gene loci will be selected. Particularly, the project explores in ESCs and derived differentiated cells the importance of transcription factor binding in the maintenance of differential DNA methylation, in allelic gene expression (of non-coding RNA) and in developmental potential.

Techniques mises en œuvre par le stagiaire :

Culture of hybrid and mono-parental (parthenogenetic and androgenetic) mouse ESCs in serum-free medium and their differentiation into different embryonic lineages. Quantitative RNA expression and DNA methylation studies. Chromatin immunoprecipitation. Comparative data analysis.

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