PT - JOURNAL ARTICLE AU - Victor Heurtier AU - Nick Owens AU - Inma Gonzalez AU - Florian Mueller AU - Caroline Proux AU - Damien Mornico AU - Philippe Clerc AU - Agnès Dubois AU - Pablo Navarro TI - The molecular logic of Nanog-induced self-renewal AID - 10.1101/374371 DP - 2018 Jan 01 TA - bioRxiv PG - 374371 4099 - http://biorxiv.org/content/early/2018/07/23/374371.short 4100 - http://biorxiv.org/content/early/2018/07/23/374371.full AB - 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 very 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.