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

Author

Listed:
  • Qian Du

    (Garvan Institute of Medical Research
    UNSW Sydney)

  • Saul A. Bert

    (Garvan Institute of Medical Research)

  • Nicola J. Armstrong

    (Murdoch University)

  • C. Elizabeth Caldon

    (UNSW Sydney
    Garvan Institute of Medical Research)

  • Jenny Z. Song

    (Garvan Institute of Medical Research)

  • Shalima S. Nair

    (Garvan Institute of Medical Research)

  • Cathryn M. Gould

    (Garvan Institute of Medical Research)

  • Phuc-Loi Luu

    (Garvan Institute of Medical Research)

  • Timothy Peters

    (Garvan Institute of Medical Research)

  • Amanda Khoury

    (Garvan Institute of Medical Research
    UNSW Sydney)

  • Wenjia Qu

    (Garvan Institute of Medical Research)

  • Elena Zotenko

    (Garvan Institute of Medical Research)

  • Clare Stirzaker

    (Garvan Institute of Medical Research
    UNSW Sydney)

  • Susan J. Clark

    (Garvan Institute of Medical Research
    UNSW Sydney)

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.

Suggested Citation

  • Qian Du & Saul A. Bert & Nicola J. Armstrong & C. Elizabeth Caldon & Jenny Z. Song & Shalima S. Nair & Cathryn M. Gould & Phuc-Loi Luu & Timothy Peters & Amanda Khoury & Wenjia Qu & Elena Zotenko & Cl, 2019. "Replication timing and epigenome remodelling are associated with the nature of chromosomal rearrangements in cancer," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08302-1
    DOI: 10.1038/s41467-019-08302-1
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    Cited by:

    1. Kevin B. Dsouza & Alexandra Maslova & Ediem Al-Jibury & Matthias Merkenschlager & Vijay K. Bhargava & Maxwell W. Libbrecht, 2022. "Learning representations of chromatin contacts using a recurrent neural network identifies genomic drivers of conformation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Adam C. Weiner & Marc J. Williams & Hongyu Shi & Ignacio Vázquez-García & Sohrab Salehi & Nicole Rusk & Samuel Aparicio & Sohrab P. Shah & Andrew McPherson, 2024. "Inferring replication timing and proliferation dynamics from single-cell DNA sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Daniel Malzl & Mihaela Peycheva & Ali Rahjouei & Stefano Gnan & Kyle N. Klein & Mariia Nazarova & Ursula E. Schoeberl & David M. Gilbert & Sara C. B. Buonomo & Michela Virgilio & Tobias Neumann & Rush, 2023. "RIF1 regulates early replication timing in murine B cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Paola Cornejo-Páramo & Veronika Petrova & Xuan Zhang & Robert S. Young & Emily S. Wong, 2024. "Emergence of enhancers at late DNA replicating regions," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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