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SIRT6 deficiency results in developmental retardation in cynomolgus monkeys

Author

Listed:
  • Weiqi Zhang

    (CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    Institute of Zoology, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Haifeng Wan

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

  • Guihai Feng

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

  • Jing Qu

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

  • Jiaqiang Wang

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

  • Yaobin Jing

    (CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ruotong Ren

    (CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Zunpeng Liu

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

  • Linlin Zhang

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

  • Zhiguo Chen

    (Xuanwu Hospital Capital Medical University)

  • Shuyan Wang

    (Xuanwu Hospital Capital Medical University)

  • Yong Zhao

    (School of Life Sciences, Sun Yat-sen University)

  • Zhaoxia Wang

    (Peking University First Hospital)

  • Yun Yuan

    (Peking University First Hospital)

  • Qi Zhou

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

  • Wei Li

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

  • Guang-Hui Liu

    (CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
    University of Chinese Academy of Sciences
    Chinese Academy of Sciences
    Xuanwu Hospital Capital Medical University)

  • Baoyang Hu

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

Abstract

SIRT6 acts as a longevity protein in rodents1,2. However, its biological function in primates remains largely unknown. Here we generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model using a CRISPR–Cas9-based approach. SIRT6-deficient monkeys die hours after birth and exhibit severe prenatal developmental retardation. SIRT6 loss delays neuronal differentiation by transcriptionally activating the long non-coding RNA H19 (a developmental repressor), and we were able to recapitulate this process in a human neural progenitor cell differentiation system. SIRT6 deficiency results in histone hyperacetylation at the imprinting control region of H19, CTCF recruitment and upregulation of H19. Our results suggest that SIRT6 is involved in regulating development in non-human primates, and may provide mechanistic insight into human perinatal lethality syndrome.

Suggested Citation

  • Weiqi Zhang & Haifeng Wan & Guihai Feng & Jing Qu & Jiaqiang Wang & Yaobin Jing & Ruotong Ren & Zunpeng Liu & Linlin Zhang & Zhiguo Chen & Shuyan Wang & Yong Zhao & Zhaoxia Wang & Yun Yuan & Qi Zhou &, 2018. "SIRT6 deficiency results in developmental retardation in cynomolgus monkeys," Nature, Nature, vol. 560(7720), pages 661-665, August.
    • Handle: RePEc:nat:nature:v:560:y:2018:i:7720:d:10.1038_s41586-018-0437-z
    DOI: 10.1038/s41586-018-0437-z
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    Cited by:

    1. Jasmin Bartl & Marco Zanini & Flavia Bernardi & Antoine Forget & Lena Blümel & Julie Talbot & Daniel Picard & Nan Qin & Gabriele Cancila & Qingsong Gao & Soumav Nath & Idriss Mahoungou Koumba & Mariet, 2022. "The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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