DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity.
Cell Rep
; 36(12): 109722, 2021 09 21.
Article
en En
| MEDLINE
| ID: mdl-34551299
ABSTRACT
DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, in particular cancer-related DNA hypomethylation, affects higher-order levels of genome architecture is still unclear. Here, using Repli-Seq, single-cell Repli-Seq, and Hi-C, we show that genome-wide methylation loss is associated with both concordant loss of replication timing precision and deregulation of 3D genome organization. Notably, we find distinct disruption in 3D genome compartmentalization, striking gains in cell-to-cell replication timing heterogeneity and loss of allelic replication timing in cancer hypomethylation models, potentially through the gene deregulation of DNA replication and genome organization pathways. Finally, we identify ectopic H3K4me3-H3K9me3 domains from across large hypomethylated domains, where late replication is maintained, which we purport serves to protect against catastrophic genome reorganization and aberrant gene transcription. Our results highlight a potential role for the methylome in the maintenance of 3D genome regulation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Genoma Humano
/
Metilación de ADN
/
Momento de Replicación del ADN
Límite:
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Australia