PH_GERMCELL · Analysis of epigenetic reprogramming during germ cell development
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-09-01 → 2007-08-31
- EU contribution
- €0
- Participants
- 1
- Scheme
- EIF
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Project objective
Many biological processes are established by transcriptional control mechanisms, which involve reversible chromatin modifications. Mainly the interplay between methylation and acetylation of histone tails defines the epigenome of a given cell type. Stem cells must maintain pluripotency, and their differentiation potential relies on the plasticity of their epigenome.The mammalian germ line originates from a group of differentiating somatic precursors, implying that developing germ cells must reprogram their epigenetic settings to enable totipotency after conception. Primordial germ cells (PGCs) undergo both, DNA demethylation and dynamic changes of repressive histone methylation marks at histones H3 and H4.Thus, PGC differentiation represents a natural system to analyze epigenetic plasticity and the established mechanisms will provide understanding of stem cell identity. The proposed study aims to define biological functions of selected histone methyltransferases (HMTs) during germ cell development. Firstly, work in the hosting institute defined histone tail methylations that are hallmarks of differentiating germ cells.Analysis of PGC-specific gene deficient animals for the respective known HMTs Ezh2 and PR-Set7 will reveal the contribution of histone methylation to germ cell development and, in particular, to epigenetic reprogramming. The underlying molecular mechanism will be investigated by microarray-based identification of direct target genes. Secondly, expression analyses identified a small group of putative HMTs that are selectively expressed in stem cell entities.We will reveal their spatiotemporal expression patterns and their histone target specificities. RNAi mediated ablation will address their function in ex vivo germ cell differentiation. Our work will reveal mechanisms of epigenetic plasticity and define principles that govern reprogramming in the transition from pluripotent progenitors to lineage specific phenotypes and vice versa.
Original text from CORDIS.
Participants
- FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH, A PART OF THE NOVARTIS RESEARCH FOUNDATIONCoordinatorCity levelSwitzerland
Links
Data: CORDIS, © European Union