Journal article
DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity
Cell Reports, Vol.36(12), Art. 109722
2021
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.
Details
- Title
- DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity
- Authors/Creators
- Q. Du (Author/Creator) - Garvan Institute of Medical ResearchG.C. Smith (Author/Creator) - Garvan Institute of Medical ResearchP.L. Luu (Author/Creator) - Garvan Institute of Medical ResearchJ.M. Ferguson (Author/Creator) - Garvan Institute of Medical ResearchN.J. Armstrong (Author/Creator) - Murdoch UniversityC.E. Caldon (Author/Creator) - Garvan Institute of Medical ResearchE.M. Campbell (Author/Creator) - Garvan Institute of Medical ResearchS.S. Nair (Author/Creator) - Garvan Institute of Medical ResearchE. Zotenko (Author/Creator) - Garvan Institute of Medical ResearchC.M. Gould (Author/Creator) - Garvan Institute of Medical ResearchM. Buckley (Author/Creator) - Garvan Institute of Medical ResearchK-M Chia (Author/Creator) - Garvan Institute of Medical ResearchN. Portman (Author/Creator) - Garvan Institute of Medical ResearchE. Lim (Author/Creator) - Garvan Institute of Medical ResearchD. Kaczorowski (Author/Creator) - Garvan Institute of Medical ResearchC-L Chan (Author/Creator) - Garvan Institute of Medical ResearchK. Barton (Author/Creator) - Garvan Institute of Medical ResearchI.W. Deveson (Author/Creator) - UNSW SydneyM.A. Smith (Author/Creator) - UNSW SydneyJ.E. Powell (Author/Creator) - Garvan Institute of Medical ResearchK. Skvortsova (Author/Creator) - Garvan Institute of Medical ResearchC. Stirzaker (Author/Creator) - Garvan Institute of Medical ResearchJ. Achinger-Kawecka (Author/Creator) - Garvan Institute of Medical ResearchS.J. Clark (Author/Creator) - Garvan Institute of Medical Research
- Publication Details
- Cell Reports, Vol.36(12), Art. 109722
- Publisher
- Elsevier Inc.
- Identifiers
- 991005541426707891
- Copyright
- © 2021 The Author(s).
- Murdoch Affiliation
- School of Mathematics, Statistics, Chemistry and Physics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.54 Molecular & Cell Biology - Genetics
- 1.54.100 Epigenetic Regulation
- Web Of Science research areas
- Cell Biology
- ESI research areas
- Molecular Biology & Genetics