H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate - Institut Pasteur Access content directly
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H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate

Abstract

Mouse Embryonic Stem (ES) cells have an inherent propensity to explore distinct gene-regulatory states associated with either self-renewal or differentiation. This property is largely dependent on ERK activity, which promotes silencing of pluripotency genes, most notably of the transcription factor Nanog . Here, we aimed at identifying repressive histone modifications that would mark the Nanog locus for inactivation in response to ERK activity. We found histone H3 lysine 9 tri-methylation (H3K9me3) focally enriched between the Nanog promoter and its −5kb enhancer. While in undifferentiated ES cells H3K9me3 at Nanog depends on ERK activity, in somatic cells it becomes ERK-independent. Moreover, upon deletion of the region harbouring H3K9me3, ES cells display reduced heterogeneity of NANOG expression, delayed commitment into differentiation and impaired ability to acquire a primitive endoderm fate. We suggest that establishment of irreversible H3K9me3 at specific master regulators allows the acquisition of particular cell fates during differentiation.
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Dates and versions

pasteur-03796516 , version 1 (22-10-2021)
pasteur-03796516 , version 2 (04-10-2022)

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Attribution - NonCommercial - NoDerivatives

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Agnès Dubois, L. Vincenti, A. Chervova, S. Vandormael-Pournin, Michel Cohen-Tannoudji, et al.. H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate. 2021. ⟨pasteur-03796516v1⟩
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