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Selective translation of epigenetic modifiers drives the developmental clock of neural stem cells

Quan Wu, Yuichi Shichino, Takaya Abe, Taeko Suetsugu, Ayaka Omori, Hiroshi Kiyonari, Shintaro Iwasaki, Fumio Matsuzaki
doi: https://doi.org/10.1101/2020.10.08.330852
Quan Wu
1Laboratory for Cell Asymmetry, RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
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  • For correspondence: quan.wu@riken.jp fumio.matsuzaki@riken.jp
Yuichi Shichino
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
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Takaya Abe
3Laboratories for Animal Resource Development and Genetic Engineering (LARGE), RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
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Taeko Suetsugu
1Laboratory for Cell Asymmetry, RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
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Ayaka Omori
1Laboratory for Cell Asymmetry, RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
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Hiroshi Kiyonari
3Laboratories for Animal Resource Development and Genetic Engineering (LARGE), RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
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Shintaro Iwasaki
2RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
4Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan
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Fumio Matsuzaki
1Laboratory for Cell Asymmetry, RIKEN Centre for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan
5Laboratory of Molecular Cell Biology and Development, Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
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  • For correspondence: quan.wu@riken.jp fumio.matsuzaki@riken.jp
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Abstract

The cerebral cortex is formed by diverse neurons generated sequentially from neural stem cells (NSCs). A clock mechanism has been suggested to underlie the temporal progression of NSCs, which is mainly defined by the transcriptome and the epigenetic state. However, what drives such a developmental clock remains elusive. We show that translational control of histone H3 trimethylation at Lys27 (H3K27me3) modifiers is part of this clock. We found that depletion of Fbl, an rRNA methyltransferase, reduces translation of both the Ezh2 methyltransferase and Kdm6b demethylase of H3K27me3 and delays progression of the NSC state. These defects are phenocopied by simultaneous inhibition of H3K27me3 methyltransferase and demethylase, indicating the role of Fbl in the genome-wide H3K27me3 pattern. Fbl selectively enhances the translation of H3K27me3 modifiers via a cap-independent mechanism. We thus propose that Fbl drives the intrinsic clock through the translational enhancement of H3K27me3 modifiers that predominantly define the NSC state.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 08, 2020.
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Selective translation of epigenetic modifiers drives the developmental clock of neural stem cells
Quan Wu, Yuichi Shichino, Takaya Abe, Taeko Suetsugu, Ayaka Omori, Hiroshi Kiyonari, Shintaro Iwasaki, Fumio Matsuzaki
bioRxiv 2020.10.08.330852; doi: https://doi.org/10.1101/2020.10.08.330852
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Selective translation of epigenetic modifiers drives the developmental clock of neural stem cells
Quan Wu, Yuichi Shichino, Takaya Abe, Taeko Suetsugu, Ayaka Omori, Hiroshi Kiyonari, Shintaro Iwasaki, Fumio Matsuzaki
bioRxiv 2020.10.08.330852; doi: https://doi.org/10.1101/2020.10.08.330852

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