Gene resistance to transcriptional reprogramming following nuclear transfer is directly mediated by multiple chromatin-repressive pathways - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecular Cell Année : 2017

Gene resistance to transcriptional reprogramming following nuclear transfer is directly mediated by multiple chromatin-repressive pathways

Résumé

Understanding the mechanism of resistance of genes to reactivation will help improve the success of nuclear reprogramming. Using mouse embryonic fibroblast nuclei with normal or reduced DNA methylation in combination with chromatin modifiers able to erase H3K9me3, H3K27me3, and H2AK119ub1 from transplanted nuclei, we reveal the basis for resistance of genes to transcriptional reprogramming by oocyte factors. A majority of genes is affected by more than one type of treatment, suggesting that resistance can require repression through multiple epigenetic mechanisms. We classify resistant genes according to their sensitivity to 11 chromatin modifier combinations, revealing the existence of synergistic as well as adverse effects of chromatin modifiers on removal of resistance. We further demonstrate that the chromatin modifier USP21 reduces resistance through its H2AK119 deubiquitylation activity. Finally, we provide evidence that H2A ubiquitylation also contributes to resistance to transcriptional reprogramming in mouse nuclear transfer embryos.
Fichier principal
Vignette du fichier
2017_Jullien_molecular cell_1.pdf (2.94 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-01607631 , version 1 (26-05-2020)

Licence

Paternité

Identifiants

Citer

Jerome Jullien, Munender Vodnala, Vincent Pasque, Mami Oikawa, Kei Miyamoto, et al.. Gene resistance to transcriptional reprogramming following nuclear transfer is directly mediated by multiple chromatin-repressive pathways. Molecular Cell, 2017, 65 (5), pp.873-884; e1-e8. ⟨10.1016/j.molcel.2017.01.030⟩. ⟨hal-01607631⟩
158 Consultations
39 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More