DAXX safeguards pericentromeric heterochromatin formation in embryonic stem cells - HAL Accéder directement au contenu
Pré-publication, Document de travail Année : 2021

DAXX safeguards pericentromeric heterochromatin formation in embryonic stem cells

Résumé

Abstract DNA methylation is essential for heterochromatin formation and repression of DNA repeat transcription, both of which are essential for genome integrity. Loss of DNA methylation is associated with disease, including cancer, but is also required for development. Alternative pathways to maintain heterochromatin are thus needed to limit DNA damage accumulation. Here, we find that DAXX, an H3.3 chaperone, protects pericentromeric heterochromatin and is essential for embryonic stem cells (ESCs) maintenance in the ground-state of pluripotency. Upon DNA demethylation-mediated damage, DAXX relocalizes to pericentromeric regions, and recruits PML and SETDB1, thereby promoting heterochromatin formation. In the absence of DAXX, the 3D-architecture and physical properties of pericentric heterochromatin are disrupted, resulting in derepression of major satellite DNA. Using epigenome editing tools, we demonstrate that H3.3, and specifically H3.3K9 modification, directly contribute to maintaining pericentromeric chromatin conformation. Altogether, our data reveal that DAXX and H3.3 unite DNA damage response and heterochromatin maintenance in ESCs.
Loading...

Dates et versions

hal-03455213, version 1 (29-11-2021)

Identifiants

Citer

Antoine Canat, Adeline Veillet, Robert Illingworth, Emmanuelle Fabre, Pierre Therizols. DAXX safeguards pericentromeric heterochromatin formation in embryonic stem cells. 2021. ⟨hal-03455213⟩
21 Consultations
0 Téléchargements
Dernière date de mise à jour le 26/06/2024
comment ces indicateurs sont-ils produits

Altmetric

Partager

Gmail Facebook Twitter LinkedIn Plus