Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer

Q. Du; S.A. Bert; N.J. Armstrong; C.E. Caldon; J.Z. Song; S.S. Nair; C.M. Gould; P-L Luu; T. Peters; A. Khoury; W. Qu; E. Zotenko; C. Stirzaker; S.J. Clark

doi:10.1038/s41467-019-08302-1

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Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer

Journal article

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Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer

Q. Du, S.A. Bert, N.J. Armstrong, C.E. Caldon, J.Z. Song, S.S. Nair, C.M. Gould, P-L Luu, T. Peters, A. Khoury, …

Nature Communications, Vol.10(1), Article No. 416

2019

DOI: https://doi.org/10.1038/s41467-019-08302-1

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Abstract

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.

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Title: Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
Authors/Creators: Q. Du (Author/Creator) - Garvan Institute of Medical Research
S.A. Bert (Author/Creator) - Garvan Institute of Medical Research
N.J. Armstrong (Author/Creator) - Murdoch University
C.E. Caldon (Author/Creator) - St Vincent's Clinic
J.Z. Song (Author/Creator) - Garvan Institute of Medical Research
S.S. Nair (Author/Creator) - Garvan Institute of Medical Research
C.M. Gould (Author/Creator) - Garvan Institute of Medical Research
P-L Luu (Author/Creator) - Garvan Institute of Medical Research
T. Peters (Author/Creator) - Garvan Institute of Medical Research
A. Khoury (Author/Creator) - Garvan Institute of Medical Research
W. Qu (Author/Creator) - Garvan Institute of Medical Research
E. Zotenko (Author/Creator) - Garvan Institute of Medical Research
C. Stirzaker (Author/Creator) - Garvan Institute of Medical Research
S.J. Clark (Author/Creator) - Garvan Institute of Medical Research
Publication Details: Nature Communications, Vol.10(1), Article No. 416
Publisher: Springer Nature
Identifiers: 991005540987707891
Murdoch Affiliation: School of Engineering and Information Technology
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: Biochemistry & Molecular Biology
ESI research areas: Molecular Biology & Genetics