TBC1D3 promotes neural progenitor proliferation by suppressing the histone methyltransferase G9a.

Autor:	Hou QQ; School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China., Xiao Q; School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, China.; University of Chinese Academy of Sciences, 100049 Beijing, China., Sun XY; School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, China.; University of Chinese Academy of Sciences, 100049 Beijing, China., Ju XC; Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, 200031 Shanghai, China., Luo ZG; School of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China. luozhg@shanghaitech.edu.cn.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Jan 15; Vol. 7 (3). Date of Electronic Publication: 2021 Jan 15 (Print Publication: 2021).
DOI:	10.1126/sciadv.aba8053
Abstrakt:	Genomic changes during human linage evolution contribute to the expansion of the cerebral cortex to allow more advanced thought processes. The hominoid-specific gene TBC1D3 displays robust capacity of promoting the generation and proliferation of neural progenitors (NPs), which are thought to contribute to cortical expansion. However, the underlying mechanisms remain unclear. Here, we found that TBC1D3 interacts with G9a, a euchromatic histone lysine N -methyltransferase, which mediates dimethylation of histone 3 in lysine 9 (H3K9me2), a suppressive mark for gene expression. TBC1D3 displayed an inhibitory role in G9a's histone methyltransferase activity. Treatment with G9a inhibitor markedly increased NP proliferation and promoted human cerebral organoid expansion, mimicking the effects caused by TBC1D3 up-regulation. By contrast, blockade of TBC1D3/G9a interaction to disinhibit G9a caused up-regulation of H3K9me2, suppressed NP proliferation, and impaired organoid development. Together, this study has demonstrated a mechanism underlying the role of a hominoid-specific gene in promoting cortical expansion. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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