PUBLICATION
Histone acetyltransferase KAT2A modulates neural stem cell differentiation and proliferation by inducing degradation of the transcription factor PAX6
- Authors
- Dong, Z., He, W., Lin, G., Chen, X., Cao, S., Guan, T., Sun, Y., Zhang, Y., Qi, M., Guo, B., Zhou, Z., Zhuo, R., Wu, R., Liu, M., Liu, Y.
- ID
- ZDB-PUB-230216-38
- Date
- 2023
- Source
- The Journal of biological chemistry 299(3): 103020 (Journal)
- Registered Authors
- Keywords
- KAT2A, Neural stem cells, PAX6, acetylation, differentiation, ubiquitination
- MeSH Terms
-
- Animals
- Cell Differentiation/physiology
- Cell Proliferation
- Histone Acetyltransferases/genetics
- Histone Acetyltransferases/metabolism
- Neural Stem Cells*/metabolism
- PAX6 Transcription Factor/genetics
- PAX6 Transcription Factor/metabolism
- Rats
- Transcription Factors/metabolism
- Zebrafish*/metabolism
- PubMed
- 36791914 Full text @ J. Biol. Chem.
Citation
Dong, Z., He, W., Lin, G., Chen, X., Cao, S., Guan, T., Sun, Y., Zhang, Y., Qi, M., Guo, B., Zhou, Z., Zhuo, R., Wu, R., Liu, M., Liu, Y. (2023) Histone acetyltransferase KAT2A modulates neural stem cell differentiation and proliferation by inducing degradation of the transcription factor PAX6. The Journal of biological chemistry. 299(3):103020.
Abstract
Neural stem cells (NSCs) proliferation and differentiation rely on proper expression and post-translational modification of transcription factors involved in the determination of cell fate. Further characterization is needed to connect modifying enzymes with their transcription factor substrates in the regulation of these processes. Here, we demonstrated that the inhibition of KAT2A, a histone acetyltransferase, leads to a phenotype of small eyes in the developing embryo of zebrafish, which is associated with enhanced proliferation and apoptosis of NSCs in zebrafish eyes. We confirmed that this phenotype is mediated by the evaluated level of PAX6 protein. We further verified that KAT2A negatively regulates PAX6 at the protein level in cultured neural stem cells of rat cerebral cortex. We revealed that PAX6 is a novel acetylation substrate of KAT2A, and the acetylation of PAX6 promotes its ubiquitination mediated by the E3 ligase RNF8 that facilitated PAX6 degradation. Our study proposes that KAT2A inhibition results in accelerated proliferation, delayed differentiation, or apoptosis, depending on the context of PAX6 dosage. Thus, the KAT2A/PAX6 axis plays an essential role to keep a balance between the self-renewal and differentiation of NSCs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping