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Replication landscape of the human genome

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  • Nataliya Petryk

    (Ecole Normale Supérieure, Institut de Biologie de l’ENS (IBENS), and Inserm U1024, and CNRS UMR 8197
    Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud
    Present address: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, Copenhagen 2200, Denmark.)

  • Malik Kahli

    (Ecole Normale Supérieure, Institut de Biologie de l’ENS (IBENS), and Inserm U1024, and CNRS UMR 8197)

  • Yves d'Aubenton-Carafa

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud)

  • Yan Jaszczyszyn

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud)

  • Yimin Shen

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud)

  • Maud Silvain

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud)

  • Claude Thermes

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud)

  • Chun-Long Chen

    (Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud)

  • Olivier Hyrien

    (Ecole Normale Supérieure, Institut de Biologie de l’ENS (IBENS), and Inserm U1024, and CNRS UMR 8197)

Abstract

Despite intense investigation, human replication origins and termini remain elusive. Existing data have shown strong discrepancies. Here we sequenced highly purified Okazaki fragments from two cell types and, for the first time, quantitated replication fork directionality and delineated initiation and termination zones genome-wide. Replication initiates stochastically, primarily within non-transcribed, broad (up to 150 kb) zones that often abut transcribed genes, and terminates dispersively between them. Replication fork progression is significantly co-oriented with the transcription. Initiation and termination zones are frequently contiguous, sometimes separated by regions of unidirectional replication. Initiation zones are enriched in open chromatin and enhancer marks, even when not flanked by genes, and often border ‘topologically associating domains’ (TADs). Initiation zones are enriched in origin recognition complex (ORC)-binding sites and better align to origins previously mapped using bubble-trap than λ-exonuclease. This novel panorama of replication reveals how chromatin and transcription modulate the initiation process to create cell-type-specific replication programs.

Suggested Citation

  • Nataliya Petryk & Malik Kahli & Yves d'Aubenton-Carafa & Yan Jaszczyszyn & Yimin Shen & Maud Silvain & Claude Thermes & Chun-Long Chen & Olivier Hyrien, 2016. "Replication landscape of the human genome," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10208
    DOI: 10.1038/ncomms10208
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    Cited by:

    1. Eri Koyanagi & Yoko Kakimoto & Tamiko Minamisawa & Fumiya Yoshifuji & Toyoaki Natsume & Atsushi Higashitani & Tomoo Ogi & Antony M. Carr & Masato T. Kanemaki & Yasukazu Daigaku, 2022. "Global landscape of replicative DNA polymerase usage in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Lorenzo Corazzi & Vivien S. Ionasz & Sergej Andrejev & Li-Chin Wang & Athanasios Vouzas & Marco Giaisi & Giulia Di Muzio & Boyu Ding & Anna J. M. Marx & Jonas Henkenjohann & Michael M. Allers & David , 2024. "Linear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Wenting Zhang & Yue Wang & Yongjie Liu & Cuifang Liu & Yizhou Wang & Lin He & Xiao Cheng & Yani Peng & Lu Xia & Xiaodi Wu & Jiajing Wu & Yu Zhang & Luyang Sun & Ping Chen & Guohong Li & Qiang Tu & Jin, 2023. "NFIB facilitates replication licensing by acting as a genome organizer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Congcong Tian & Jiaqi Zhou & Xinran Li & Yuan Gao & Qing Wen & Xing Kang & Nan Wang & Yuan Yao & Jiuhang Jiang & Guibing Song & Tianjun Zhang & Suili Hu & JingYi Liao & Chuanhe Yu & Zhiquan Wang & Xia, 2023. "Impaired histone inheritance promotes tumor progression," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Dashiell J. Massey & Amnon Koren, 2022. "High-throughput analysis of single human cells reveals the complex nature of DNA replication timing control," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Kate E. Coleman & Yandong Yin & Sarah Kit Leng Lui & Sarah Keegan & David Fenyo & Duncan J. Smith & Eli Rothenberg & Tony T. Huang, 2022. "USP1-trapping lesions as a source of DNA replication stress and genomic instability," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    7. 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.

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