The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells

Victor Heurtier, Nick Owens, Inma Gonzalez, Florian Mueller, Caroline Proux, Damien Mornico, Philippe Clerc, Agnes Dubois and Pablo Navarro ()
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Victor Heurtier: Institut Pasteur, CNRS UMR3738
Nick Owens: Institut Pasteur, CNRS UMR3738
Inma Gonzalez: Institut Pasteur, CNRS UMR3738
Florian Mueller: Institut Pasteur, CNRS UMR 3691
Caroline Proux: Institut Pasteur
Damien Mornico: Institut Pasteur, CNRS USR 3756
Philippe Clerc: Institut Pasteur, CNRS UMR3738
Agnes Dubois: Institut Pasteur, CNRS UMR3738
Pablo Navarro: Institut Pasteur, CNRS UMR3738

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Transcription factor networks, together with histone modifications and signalling pathways, underlie the establishment and maintenance of gene regulatory architectures associated with the molecular identity of each cell type. However, how master transcription factors individually impact the epigenomic landscape and orchestrate the behaviour of regulatory networks under different environmental constraints is only partially understood. Here, we show that the transcription factor Nanog deploys multiple distinct mechanisms to enhance embryonic stem cell self-renewal. In the presence of LIF, which fosters self-renewal, Nanog rewires the pluripotency network by promoting chromatin accessibility and binding of other pluripotency factors to thousands of enhancers. In the absence of LIF, Nanog blocks differentiation by sustaining H3K27me3, a repressive histone mark, at developmental regulators. Among those, we show that the repression of Otx2 plays a preponderant role. Our results underscore the versatility of master transcription factors, such as Nanog, to globally influence gene regulation during developmental processes.

Date: 2019
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DOI: 10.1038/s41467-019-09041-z

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