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Analysis of the gene regulatory network controlling ES cell identity

Ziel

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.

Wissenschaftliches Gebiet (EuroSciVoc)

Programm/Programme

Thema/Themen

Aufforderung zur Vorschlagseinreichung

FP7-PEOPLE-2009-IEF
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

MC-IEF - Intra-European Fellowships (IEF)

Koordinator

THE UNIVERSITY OF EDINBURGH
EU-Beitrag
€ 181 103,20
Adresse
OLD COLLEGE, SOUTH BRIDGE
EH8 9YL Edinburgh
Vereinigtes Königreich
Region
Scotland Eastern Scotland Edinburgh
Aktivitätstyp
Higher or Secondary Education Establishments
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