Unravelling specificity of epi-metabolic regulation in mouse development

Title	Unravelling specificity of epi-metabolic regulation in mouse development
Acronym	ChroMeta
Website	https://renew.ku.dk/research/reseach-groups/zylicz-group/
Start date	2023-12-01
End date	2028-11-30
Sponsor	European Research Council - Starting Grant (ERC-StG)
Institution	University of Copenhagen

Associated cell lines

Project Description

When environment of the embryo changes or when development progresses metabolic reactions are rapidly affected. These alterations to chemical reactions are coupled to epigenetic memory. However, without mechanistic data on how this coupling occurs it is difficult to understand how normal embryogenesis can proceed. This project will elucidate how metabolic changes result in specific epigenetic outcomes and address the function of such regulation. As a model we will use mouse implantation and human ESC, a process tightly linked to dramatic alterations to chromatin and transcription. We found that this is also associated with extensive metabolic rewiring and that disrupting metabolic flows results in both lineage-specific and mark-specific changes to chromatin. While multiple studies uncovered that metabolism fuels chromatin modifiers with co-factors, the fundamental biological question of how specificity is achieved remains unanswered. This project will form a framework of how future studies can mechanistically unravel intertwined regulatory processes and assess the role of environment and nutrition in early pregnancy.