Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice, Nat Commun, 9(1):1261, 28 Mar 2018
发布时间：2018年05月07日
Nature Communications, 9(1):1261，28 Mar 2018，DOI: 10.1016/j.cell.2018.04.023
Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice
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 Zhu, Luyun He, Yong Tian & Zusen Fan
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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Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice, Nat Commun, 9(1):1261, 28 Mar 2018
Nature Communications, 9(1):1261，28 Mar 2018，DOI: 10.1016/j.cell.2018.04.023
Klf4 glutamylation is required for cell reprogramming and early embryonic development in mice
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 Zhu, Luyun He, Yong Tian & Zusen Fan
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.
文章链接：https://www.nature.com/articles/s41467-018-03008-2