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Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice

Author

Listed:
  • Buqing Ye

    (Chinese Academy of Sciences)

  • Benyu Liu

    (Chinese Academy of Sciences)

  • Lu Hao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiaoxiao Zhu

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Liuliu Yang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shuo Wang

    (Chinese Academy of Sciences)

  • Pengyan Xia

    (Chinese Academy of Sciences)

  • Ying Du

    (Chinese Academy of Sciences)

  • Shu Meng

    (Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Guanling Huang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xiwen Qin

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yanying Wang

    (Chinese Academy of Sciences)

  • Xinlong Yan

    (Chinese Academy of Sciences)

  • Chong Li

    (Chinese Academy of Sciences)

  • Junfeng Hao

    (Chinese Academy of Sciences)

  • Pingping Zhu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Luyun He

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yong Tian

    (Chinese Academy of Sciences)

  • Zusen Fan

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Temporal and spatial-specific regulation of pluripotency networks is largely dependent on the precise modifications of core transcription factors. Misregulation of glutamylation is implicated in severe physiological abnormalities. However, how glutamylation regulates cell reprogramming and pluripotency networks remains elusive. Here we show that cytosolic carboxypeptidases 1 (CCP1) or CCP6 deficiency substantially promotes induced pluripotent cell (iPSC) induction and pluripotency of embryonic stem cells (ESCs). Klf4 polyglutamylation at Glu381 by tubulin tyrosine ligase-like 4 (TTLL4) and TTLL1 during cell reprogramming impedes its lysine 48-linked ubiquitination and sustains Klf4 stability. Klf4-E381A knockin mice display impaired blastocyst development and embryonic lethality. Deletion of TTLL4 or TTLL1 abrogates cell reprogramming and early embryogenesis. Thus, Klf4 polyglutamylation plays a critical role in the regulation of cell reprogramming and pluripotency maintenance.

Suggested Citation

  • Buqing Ye & Benyu Liu & Lu Hao & Xiaoxiao Zhu & Liuliu Yang & Shuo Wang & Pengyan Xia & Ying Du & Shu Meng & Guanling Huang & Xiwen Qin & Yanying Wang & Xinlong Yan & Chong Li & Junfeng Hao & Pingping, 2018. "Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03008-2
    DOI: 10.1038/s41467-018-03008-2
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