2. Academic Validation
  3. Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice

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

  • Nat Commun. 2018 Mar 28;9(1):1261. doi: 10.1038/s41467-018-03008-2.
Buqing Ye 1,  Benyu Liu 1,  Lu Hao 1 2,  Xiaoxiao Zhu 3 4,  Liuliu Yang 1 2,  Shuo Wang 1,  Pengyan Xia 1,  Ying Du 1,  Shu Meng 3 4,  Guanling Huang 1 2,  Xiwen Qin 1 2,  Yanying Wang 1,  Xinlong Yan 1,  Chong Li 1,  Junfeng Hao 3,  Pingping Zhu 1 2,  Luyun He 1 2,  Yong Tian 5,  Zusen Fan 6 7
Affiliations

Affiliations

  • 1 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Laboratory Animal Center, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 4 Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  • 5 Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ytian@ibp.ac.cn.
  • 6 Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. fanz@moon.ibp.ac.cn.
  • 7 University of Chinese Academy of Sciences, Beijing, 100049, China. fanz@moon.ibp.ac.cn.
PMID: 29593216 DOI: 10.1038/s41467-018-03008-2
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.

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