Back to Search
Start Over
DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity
- Source :
- Cell Reports, Vol 36, Iss 12, Pp 109722-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Summary: 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.
- Subjects :
- DNA (Cytosine-5-)-Methyltransferase 1
DNA Replication Timing
QH301-705.5
epigenome
Gene Expression
replication timing
Computational biology
single-cell sequencing
Biology
Genome
General Biochemistry, Genetics and Molecular Biology
Histones
Cell Line, Tumor
Databases, Genetic
Humans
Biology (General)
Genomic organization
Replication timing
DNA methylation
Genome, Human
DNA replication
Sequence Analysis, DNA
Epigenome
chromatin
allele-specific replication
DNA hypomethylation
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 36
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....fd76a798d3c57fdab816399ea5646f54