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

Luca Fagnocchi, Alessandro Cherubini, Hiroshi Hatsuda, Alessandra Fasciani, Stefania Mazzoleni, Vittoria Poli, Valeria Berno, Riccardo L. Rossi, Rolland Reinbold, Max Endele, Timm Schroeder, Marina Rocchigiani, Żaneta Szkarłat, Salvatore Oliviero, Stephen Dalton and Alessio Zippo ()
Additional contact information
Luca Fagnocchi: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Alessandro Cherubini: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Hiroshi Hatsuda: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Alessandra Fasciani: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Stefania Mazzoleni: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Vittoria Poli: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Valeria Berno: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Riccardo L. Rossi: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’
Rolland Reinbold: Institute of Biomedical Technologies, National Research Council
Max Endele: ETH Zurich
Timm Schroeder: ETH Zurich
Marina Rocchigiani: Chimica e Farmacia Università di Siena
Żaneta Szkarłat: Chimica e Farmacia Università di Siena
Salvatore Oliviero: Chimica e Farmacia Università di Siena
Stephen Dalton: University of Georgia
Alessio Zippo: Fondazione Istituto Nazionale di Genetica Molecolare ‘Romeo ed Enrica Invernizzi’

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms11903 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11903

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms11903

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().