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Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
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Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
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Journal Article
Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
2019
Overview
DNA replication timing is known to facilitate the establishment of the epigenome, however, the intimate connection between replication timing and changes to the genome and epigenome in cancer remain largely uncharacterised. Here, we perform Repli-Seq and integrated epigenome analyses and demonstrate that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing. A subset of altered replication timing domains are conserved across cancers from different tissue origins. Notably, late-replicating regions in cancer cells display a loss of DNA methylation, and a switch in heterochromatin features from H3K9me3-marked constitutive to H3K27me3-marked facultative heterochromatin. Finally, analysis of 214 prostate and 35 breast cancer genomes reveal that late-replicating regions are prone to
cis
and early-replication to
trans
chromosomal rearrangements. Together, our data suggests that the nature of chromosomal rearrangement in cancer is related to the spatial and temporal positioning and altered epigenetic states of early-replicating compared to late-replicating loci.
The connection between DNA replication timing and changes that occur to the epigenome in cancer are still poorly understood. Here, the authors perform Repli-Seq and integrated epigenome analyses and find that genomic regions that undergo long-range epigenetic deregulation in prostate cancer also show concordant differences in replication timing.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/15
/ 45/23
/ 45/91
/ 631/67
/ Cancer
/ Deoxyribonuclease I - analysis
/ DNA
/ DNA Replication Timing - physiology
/ Domains
/ Epigenesis, Genetic - physiology
/ Female
/ Gene Expression Regulation, Neoplastic
/ Genome
/ Genomes
/ Genomics
/ Humanities and Social Sciences
/ Humans
/ Male
/ Prostate
/ Science
