RRC ID 63471
Author Huang J, Gujar MR, Deng Q, Y Chia S, Li S, Tan P, Sung WK, Wang H.
Title Histone lysine methyltransferase Pr-set7/SETD8 promotes neural stem cell reactivation.
Journal EMBO Rep
Abstract The ability of neural stem cells (NSCs) to switch between quiescence and proliferation is crucial for brain development and homeostasis. Increasing evidence suggests that variants of histone lysine methyltransferases including KMT5A are associated with neurodevelopmental disorders. However, the function of KMT5A/Pr-set7/SETD8 in the central nervous system is not well established. Here, we show that Drosophila Pr-Set7 is a novel regulator of NSC reactivation. Loss of function of pr-set7 causes a delay in NSC reactivation and loss of H4K20 monomethylation in the brain. Through NSC-specific in vivo profiling, we demonstrate that Pr-set7 binds to the promoter region of cyclin-dependent kinase 1 (cdk1) and Wnt pathway transcriptional co-activator earthbound1/jerky (ebd1). Further validation indicates that Pr-set7 is required for the expression of cdk1 and ebd1 in the brain. Similar to Pr-set7, Cdk1 and Ebd1 promote NSC reactivation. Finally, overexpression of Cdk1 and Ebd1 significantly suppressed NSC reactivation defects observed in pr-set7-depleted brains. Therefore, Pr-set7 promotes NSC reactivation by regulating Wnt signaling and cell cycle progression. Our findings may contribute to the understanding of mammalian KMT5A/PR-SET7/SETD8 during brain development.
Volume 22(4)
Pages e50994
Published 2021-4-7
DOI 10.15252/embr.202050994
PMID 33565211
PMC PMC8024890
MeSH Animals CDC2 Protein Kinase Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Histones* Neural Stem Cells* / metabolism
IF 7.497
Resource
Drosophila 3307R-3