PT - JOURNAL ARTICLE AU - Quan Wu AU - Yuichi Shichino AU - Takaya Abe AU - Taeko Suetsugu AU - Ayaka Omori AU - Hiroshi Kiyonari AU - Shintaro Iwasaki AU - Fumio Matsuzaki TI - Selective translation of epigenetic modifiers drives the developmental clock of neural stem cells AID - 10.1101/2020.10.08.330852 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.10.08.330852 4099 - http://biorxiv.org/content/early/2020/10/08/2020.10.08.330852.short 4100 - http://biorxiv.org/content/early/2020/10/08/2020.10.08.330852.full AB - 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 StatementThe authors have declared no competing interest.