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Séminaire

Molecular regulation and function of Nanog in mouse ES cells

Dr Pablo NAVARRO GIL
Institut Pasteur, Paris

mercredi 25 avril 2018 - 11h00 - Auditorium, IGBMC
Invité(e) par Equipe L. Tora

Nanog was identified 15 years ago and is generally considered to form, together with Oct4 and Sox2, the core of the pluripotency gene regulatory network. Hence, Nanog has been the focus of extensive research to elucidate its role in vivo, in ES cells and during reprogramming. Surprisingly, and despite the initial promises hold by this TF, Nanog is not to strictly required for the maintenance or induction of pluripotency in vitro, even though it is essential to specify the epiblast during mouse embryogenesis. Its importance in ES cell biology is however underscored by its strong capacity to drive self-renewal, even in the absence of the otherwise obligatory LIF cytokine or inhibitors of signaling molecules associated with differentiation. Moreover, Nanog expression is dynamically regulated in ES cells, leading to transcription fluctuations that reflect the global activity of the pluripotency network, with low levels of Nanog being associated with an increased propensity to differentiate. Overall, while we have a relatively good knowledge regarding the biological role of Nanog, the underlying mechanisms are not fully understood and are currently centered on the connection of Nanog with other TFs: Nanog activates the expression of a small set of pro-self-renewal factors, such as Klf4 and Esrrb, and represses key regulators of differentiation like Gata6 and Otx2. However, whether other gene regulatory processes, such as histone methylation, are involved in Nanog regulation and function remains largely unknown. I will present our work investigating how H3K9me3 and H3K27me3 control Nanog and its targets, respectively, in a signaling-dependent manner.

 

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