Histone Lysine Methyltransferase Pr-set7/SETD8 Promotes Neural Stem Cell Reactivation

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2021 Feb 10

PMID 33565211

Citations 14

Authors

Jiawen Huang

Mahekta R Gujar

Qiannan Deng

Sook Y Chia

Song Li

Patrick Tan

Wing-Kin Sung

Hongyan Wang

Affiliations

Soon will be listed here.

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.

Citing Articles

SUMOylation of Warts kinase promotes neural stem cell reactivation.

Gao Y, Tan Y, Lin J, Chew L, Aung H, Palliyana B Nat Commun. 2024; 15(1):8557.

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Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling.

Lin K, Gujar M, Lin J, Ding W, Huang J, Gao Y Sci Adv. 2024; 10(30):eadl4694.

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Set8 and L(3)mbt function in gene expression independently of histone H4 lysine 20 methylation.

Crain A, Butler M, Hill C, Huynh M, McGinty R, Duronio R Genes Dev. 2024; 38(9-10):455-472.

PMID: 38866557 PMC: 11216177. DOI: 10.1101/gad.351698.124.

Quiescent Adult Neural Stem Cells: Developmental Origin and Regulatory Mechanisms.

Meng H, Huan Y, Zhang K, Yi X, Meng X, Kang E Neurosci Bull. 2024; 40(9):1353-1363.

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A fly's eye view of quiescent neural stem cells.

Gujar M, Wang H Oxf Open Neurosci. 2024; 1:kvac001.

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