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

Quan Wu (), Yuichi Shichino, Takaya Abe, Taeko Suetsugu, Ayaka Omori, Hiroshi Kiyonari, Shintaro Iwasaki and Fumio Matsuzaki ()
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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
Fumio Matsuzaki: RIKEN Centre for Biosystems Dynamics Research

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28097-y

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