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

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...

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Autores principales: Du, Qian, Bert, Saul A., Armstrong, Nicola J., Caldon, C. Elizabeth, Song, Jenny Z., Nair, Shalima S., Gould, Cathryn M., Luu, Phuc-Loi, Peters, Timothy, Khoury, Amanda, Qu, Wenjia, Zotenko, Elena, Stirzaker, Clare, Clark, Susan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345877/
https://www.ncbi.nlm.nih.gov/pubmed/30679435
http://dx.doi.org/10.1038/s41467-019-08302-1
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author Du, Qian
Bert, Saul A.
Armstrong, Nicola J.
Caldon, C. Elizabeth
Song, Jenny Z.
Nair, Shalima S.
Gould, Cathryn M.
Luu, Phuc-Loi
Peters, Timothy
Khoury, Amanda
Qu, Wenjia
Zotenko, Elena
Stirzaker, Clare
Clark, Susan J.
author_facet Du, Qian
Bert, Saul A.
Armstrong, Nicola J.
Caldon, C. Elizabeth
Song, Jenny Z.
Nair, Shalima S.
Gould, Cathryn M.
Luu, Phuc-Loi
Peters, Timothy
Khoury, Amanda
Qu, Wenjia
Zotenko, Elena
Stirzaker, Clare
Clark, Susan J.
author_sort Du, Qian
collection PubMed
description 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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spelling pubmed-63458772019-01-28 Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer Du, Qian Bert, Saul A. Armstrong, Nicola J. Caldon, C. Elizabeth Song, Jenny Z. Nair, Shalima S. Gould, Cathryn M. Luu, Phuc-Loi Peters, Timothy Khoury, Amanda Qu, Wenjia Zotenko, Elena Stirzaker, Clare Clark, Susan J. Nat Commun Article 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. Nature Publishing Group UK 2019-01-24 /pmc/articles/PMC6345877/ /pubmed/30679435 http://dx.doi.org/10.1038/s41467-019-08302-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Du, Qian
Bert, Saul A.
Armstrong, Nicola J.
Caldon, C. Elizabeth
Song, Jenny Z.
Nair, Shalima S.
Gould, Cathryn M.
Luu, Phuc-Loi
Peters, Timothy
Khoury, Amanda
Qu, Wenjia
Zotenko, Elena
Stirzaker, Clare
Clark, Susan J.
Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
title Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
title_full Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
title_fullStr Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
title_full_unstemmed Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
title_short Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
title_sort replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345877/
https://www.ncbi.nlm.nih.gov/pubmed/30679435
http://dx.doi.org/10.1038/s41467-019-08302-1
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