A Myc-driven self-reinforcing regulatory network maintains mouse embryonic stem cell identity

Open access
Date
2016-06Type
- Journal Article
Citations
Cited 41 times in
Web of Science
Cited 41 times in
Scopus
ETH Bibliography
yes
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Abstract
Stem cell identity depends on the integration of extrinsic and intrinsic signals, which directly influence the maintenance of their epigenetic state. Although Myc transcription factors play a major role in stem cell self-renewal and pluripotency, their integration with signalling pathways and epigenetic regulators remains poorly defined. We addressed this point by profiling the gene expression and epigenetic pattern in ESCs whose growth depends on conditional Myc activity. Here we show that Myc potentiates the Wnt/β-catenin signalling pathway, which cooperates with the transcriptional regulatory network in sustaining ESC self-renewal. Myc activation results in the transcriptional repression of Wnt antagonists through the direct recruitment of PRC2 on these targets. The consequent potentiation of the autocrine Wnt/β-catenin signalling induces the transcriptional activation of the endogenous Myc family members, which in turn activates a Myc-driven self-reinforcing circuit. Thus, our data unravel a Myc-dependent self-propagating epigenetic memory in the maintenance of ESC self-renewal capacity. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000117698Publication status
publishedExternal links
Journal / series
Nature CommunicationsVolume
Pages / Article No.
Publisher
Nature Publishing GroupOrganisational unit
03992 - Schroeder, Timm / Schroeder, Timm
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Show all metadata
Citations
Cited 41 times in
Web of Science
Cited 41 times in
Scopus
ETH Bibliography
yes
Altmetrics