H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Development (Cambridge, England) Année : 2022

H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate

Résumé

Mouse embryonic stem cells have an inherent propensity to explore gene regulatory states associated with either self-renewal or differentiation. This property depends on ERK, which downregulates pluripotency genes such as Nanog. Here, we aimed at identifying repressive histone modifications that would mark Nanog for inactivation in response to ERK activity. We found that the transcription factor ZFP57, which binds methylated DNA to nucleate heterochromatin, is recruited upstream of Nanog, within a region enriched for histone H3 lysine 9 tri-methylation (H3K9me3). Whereas before differentiation H3K9me3 at Nanog depends on ERK, in somatic cells it becomes independent of ERK. Moreover, the loss of H3K9me3 at Nanog, induced by deleting the region or by knocking out DNA methyltransferases or Zfp57, is associated with reduced heterogeneity of NANOG, delayed commitment into differentiation and impaired ability to acquire a primitive endoderm fate. Hence, a network axis centred on DNA methylation, ZFP57 and H3K9me3 links Nanog regulation to ERK activity for the timely establishment of new cell identities. We suggest that establishment of irreversible H3K9me3 at specific master regulators allows the acquisition of particular cell fates during differentiation.
Fichier principal
Vignette du fichier
dev201074.pdf (4.81 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

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

Licence

Paternité

Identifiants

Citer

Agnès Dubois, Loris Vincenti, Almira Chervova, Maxim Greenberg, Sandrine Vandormael-Pournin, et al.. H3K9 tri-methylation at Nanog times differentiation commitment and enables the acquisition of primitive endoderm fate. Development (Cambridge, England), 2022, 149 (17), pp.dev201074. ⟨10.1242/dev.201074⟩. ⟨pasteur-03796516v2⟩
66 Consultations
68 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More