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H2A.Z facilitates licensing and activation of early replication origins

Author

Listed:
  • Haizhen Long

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Liwei Zhang

    (Institute of Biophysics, Chinese Academy of Sciences)

  • Mengjie Lv

    (Institute of Biophysics, Chinese Academy of Sciences)

  • Zengqi Wen

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Wenhao Zhang

    (Tsinghua University)

  • Xiulan Chen

    (University of Chinese Academy of Sciences
    Institute of Biophysics, Chinese Academy of Sciences)

  • Peitao Zhang

    (Tianjin Medical University)

  • Tongqing Li

    (Peking University)

  • Luyuan Chang

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Caiwei Jin

    (University of Chinese Academy of Sciences
    Institute of Biophysics, Chinese Academy of Sciences)

  • Guozhao Wu

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xi Wang

    (Capital Medical University)

  • Fuquan Yang

    (University of Chinese Academy of Sciences
    Institute of Biophysics, Chinese Academy of Sciences)

  • Jianfeng Pei

    (Peking University)

  • Ping Chen

    (Institute of Biophysics, Chinese Academy of Sciences)

  • Raphael Margueron

    (PSL Research University)

  • Haiteng Deng

    (Tsinghua University)

  • Mingzhao Zhu

    (University of Chinese Academy of Sciences
    Institute of Biophysics, Chinese Academy of Sciences)

  • Guohong Li

    (Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

DNA replication is a tightly regulated process that ensures the precise duplication of the genome during the cell cycle1. In eukaryotes, the licensing and activation of replication origins are regulated by both DNA sequence and chromatin features2. However, the chromatin-based regulatory mechanisms remain largely uncharacterized. Here we show that, in HeLa cells, nucleosomes containing the histone variant H2A.Z are enriched with histone H4 that is dimethylated on its lysine 20 residue (H4K20me2) and with bound origin-recognition complex (ORC). In vitro studies show that H2A.Z-containing nucleosomes bind directly to the histone lysine methyltransferase enzyme SUV420H1, promoting H4K20me2 deposition, which is in turn required for ORC1 binding. Genome-wide studies show that signals from H4K20me2, ORC1 and nascent DNA strands co-localize with H2A.Z, and that depletion of H2A.Z results in decreased H4K20me2, ORC1 and nascent-strand signals throughout the genome. H2A.Z-regulated replication origins have a higher firing efficiency and early replication timing compared with other origins. Our results suggest that the histone variant H2A.Z epigenetically regulates the licensing and activation of early replication origins and maintains replication timing through the SUV420H1–H4K20me2–ORC1 axis.

Suggested Citation

  • Haizhen Long & Liwei Zhang & Mengjie Lv & Zengqi Wen & Wenhao Zhang & Xiulan Chen & Peitao Zhang & Tongqing Li & Luyuan Chang & Caiwei Jin & Guozhao Wu & Xi Wang & Fuquan Yang & Jianfeng Pei & Ping Ch, 2020. "H2A.Z facilitates licensing and activation of early replication origins," Nature, Nature, vol. 577(7791), pages 576-581, January.
  • Handle: RePEc:nat:nature:v:577:y:2020:i:7791:d:10.1038_s41586-019-1877-9
    DOI: 10.1038/s41586-019-1877-9
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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. Aina Maria Mas & Enrique Goñi & Igor Ruiz de los Mozos & Aida Arcas & Luisa Statello & Jovanna González & Lorea Blázquez & Wei Ting Chelsea Lee & Dipika Gupta & Álvaro Sejas & Shoko Hoshina & Alexandr, 2023. "ORC1 binds to cis-transcribed RNAs for efficient activation of replication origins," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Qiliang Ding & Matthew M. Edwards & Ning Wang & Xiang Zhu & Alexa N. Bracci & Michelle L. Hulke & Ya Hu & Yao Tong & Joyce Hsiao & Christine J. Charvet & Sulagna Ghosh & Robert E. Handsaker & Kevin Eg, 2021. "The genetic architecture of DNA replication timing in human pluripotent stem cells," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    4. Sai Li & Michael R. Wasserman & Olga Yurieva & Lu Bai & Michael E. O’Donnell & Shixin Liu, 2022. "Nucleosome-directed replication origin licensing independent of a consensus DNA sequence," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. 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.

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