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Selective translation of epigenetic modifiers affects the temporal pattern and differentiation of neural stem cells

Author

Listed:
  • Quan Wu

    (RIKEN Centre for Biosystems Dynamics Research)

  • Yuichi Shichino

    (RIKEN Cluster for Pioneering Research)

  • Takaya Abe

    (RIKEN Centre for Biosystems Dynamics Research)

  • Taeko Suetsugu

    (RIKEN Centre for Biosystems Dynamics Research)

  • Ayaka Omori

    (RIKEN Centre for Biosystems Dynamics Research)

  • Hiroshi Kiyonari

    (RIKEN Centre for Biosystems Dynamics Research)

  • Shintaro Iwasaki

    (RIKEN Cluster for Pioneering Research
    The University of Tokyo)

  • Fumio Matsuzaki

    (RIKEN Centre for Biosystems Dynamics Research
    Kyoto University)

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 in Lys27 (H3K27me3) modifiers is part of this clock. We find that depletion of Fbl, an rRNA methyltransferase, reduces translation of both Ezh2 methyltransferase and Kdm6b demethylase of H3K27me3 and delays the progression of the NSC state. These defects are partially phenocopied by simultaneous inhibition of H3K27me3 methyltransferase and demethylase, indicating the role of Fbl in the genome-wide H3K27me3 pattern. Therefore, we propose that Fbl drives the intrinsic clock through the translational enhancement of the H3K27me3 modifiers that predominantly define the NSC state.

Suggested Citation

  • Quan Wu & Yuichi Shichino & Takaya Abe & Taeko Suetsugu & Ayaka Omori & Hiroshi Kiyonari & Shintaro Iwasaki & Fumio Matsuzaki, 2022. "Selective translation of epigenetic modifiers affects the temporal pattern and differentiation of neural stem cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28097-y
    DOI: 10.1038/s41467-022-28097-y
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