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FUGE-Funksjonell genomforskn.i Norg

zEPISTEM: DEFINING STEMNESS BY ASSESSING THE EPIGENETIC BASIS OF PLURIPOTENCY IN EMBRYONIC STEM CELLS OF ZEBRAFISH

Tildelt: kr 5,3 mill.

Chromatin organization around active or repressed genes starts to be elucidated, but the packaging of a gene into a chromatin structure compatible with potential for transcription, such as in a pluripotent cell, is largely unknown. The zEPISTEM research p rogram aims at identifying novel gene markers of pluripotency on the basis of their epigenetic profile in zebrafish. The hypothesis is that the premise for pluripotency resides in a unique chromatin state imposed by combinatorial DNA methylation and histo ne modifications. Relying on state-of-art epigenetic and genomics analyses of pluripotency and lineage commitment genes in zebrafish embryonic stem cells (ESCs), the scientific objective is to identify novel predictors of pluripotency and lineage-commitme nt. The technical objective is to implement ultra high throughput sequencing (UTS) in combination with epigenetic tools to set up an epigenomics technology pole in Oslo and Norway. Work program (WP) 1 defines the molecular basis of pluripotency in zebrafi sh ESCs through an epigenetic analysis of genes known or predicted to be associated with pluripotency. The data will lead to a pluripotency early prediction model, onto which WP2 and WP3 build on the identification, through different genome-wide epigeneti c approaches (array-based and UTS-based assays), of novel predictors of pluripotency in zebrafish. In silico work in WP3 will relate the zebrafish findings to available data in human ESCs, bringing a systems biology component to the project. The PIs exper tise in stem cell biology, epigenetics and zebrafish genomics will be supported by three FUGE platforms, the UTS Facility, and collaborations to create top-competence in stem cell epigenomics.

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FUGE-Funksjonell genomforskn.i Norg