Objective
Self-renewal of embryonic stem (ES) cells depends on the activity of a network of transcription factors at the centre of which lies the triumvirate of Nanog, Oct4 and Sox2 that bind together to a multitude of target genes to either activate or repress their expression. Nanog was initially isolated by the host laboratory on the basis that elevating its expression increased ES cell self-renewal efficiency. Surprisingly however, the host laboratory further demonstrated that ES cells continue to self-renew in the absence of Nanog, albeit with dramatically reduced efficiency. Moreover, Nanog is not expressed uniformly within the Oct4/Sox2-expressing undifferentiated population. Instead, ES cells fluctuate between a state in which Nanog protein levels are low or absent, associated with a poor self-renewal efficiency, and a state in which Nanog levels are high, associated with a high self-renewal efficiency. In order to shed light upon the means by which these fluctuations direct altered cellular functions, we propose a project with the specific aims of: (i) determining the gene expression profile in ES cells expressing distinct forms of Nanog, (ii) analysing the co-dependency of chromatin binding by Nanog, Oct4 and Sox2 at relevant target genes, and (iii) test the functional importance of the most relevant Nanog responsiveness genes.
Fields of science
Topic(s)
Call for proposal
FP7-PEOPLE-2009-IEF
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Funding Scheme
MC-IEF - Intra-European Fellowships (IEF)Coordinator
EH8 9YL Edinburgh
United Kingdom