Objetivo The lack of a quantitative framework around the dynamics of gene expression and its determinants represents a major hurdle for capturing transcription regulation into regulatory models. Embryonic Stem Cells (ESC) provide an excellent cellular model to quantitatively define the principles of gene regulation at the biochemical and (epi)genetic level. In SysStemCell, I will focus on two distinct mouse pluripotent cell states. My recent studies have shown that the epigenome and transcriptome of ESCs maintained in serum-free medium complemented with two kinase inhibitors and LIF (‘2i ESC’) are distinct from classical ESCs cultured in the presence of serum and LIF (‘serum ESC’). Importantly, the 2i ESCs reflect pre-implantation stage ICM cells whereas the widely studied serum cells reflect post-implantation ESCs. These two distinct pluripotent states are interconvertible in vitro, providing an unique and accessible model to explore the regulation of the pre- to post-implantation phase of early embryonic development. I will combine state-of-the-art proteomics and chromatin-based methods, including a novel in vivo UV femtosecond laser crosslinking approach, and in depths bioinformatics in an iterative manner to define the full compendium of transcription (co)factors (TF) and TF-modules that define the two cell states. The dynamics of long- and short-range interactions between these modules will be assessed and correlated with the epigenetic state and chromatin structure. Novel and existing factors will be assessed for their role in differentiation from 2i to serum and reverse programming using knockout and forced expression strategies. Collectively, my studies will provide an invaluable resource for the community and a deep insight in the mechanisms and general principles that orchestrate gene expression in particular in the hitherto unexplored transition at implantation during early mouse development. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesphysical sciencesopticslaser physics Programa(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) ERC-AG-LS2 - ERC Advanced Grant - Genetics, Genomics, Bioinformatics and Systems Biology Convocatoria de propuestas ERC-2013-ADG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida STICHTING RADBOUD UNIVERSITEIT Aportación de la UE € 2 500 000,00 Dirección HOUTLAAN 4 6525 XZ Nijmegen Países Bajos Ver en el mapa Región Oost-Nederland Gelderland Arnhem/Nijmegen Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Geurt Van Renselaar (Mr.) Investigador principal Hendrik Gerard Stunnenberg (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (1) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo STICHTING RADBOUD UNIVERSITEIT Países Bajos Aportación de la UE € 2 500 000,00 Dirección HOUTLAAN 4 6525 XZ Nijmegen Ver en el mapa Región Oost-Nederland Gelderland Arnhem/Nijmegen Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Geurt Van Renselaar (Mr.) Investigador principal Hendrik Gerard Stunnenberg (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
