TBC1D3 promotes neural progenitor proliferation by suppressing the histone methyltransferase G9a
Autor: | Zhen-Ge Luo, Qi Xiao, Xiang-Chun Ju, Xin-Yao Sun, Qiong-Qiong Hou |
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Rok vydání: | 2021 |
Předmět: |
Histone methyltransferase activity
Histones 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Proto-Oncogene Proteins Gene expression Organoid medicine Humans Research Articles Cell Proliferation 030304 developmental biology 0303 health sciences Multidisciplinary biology Chemistry Lysine GTPase-Activating Proteins SciAdv r-articles Histone-Lysine N-Methyltransferase Methylation Cell biology Histone medicine.anatomical_structure Cerebral cortex Histone methyltransferase Histone Methyltransferases biology.protein 030217 neurology & neurosurgery Research Article Developmental Biology Cerebral organoid |
Zdroj: | Science Advances |
ISSN: | 2375-2548 |
Popis: | A hominoid-specific gene promotes cortical expansion via regulating histone modification. 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. |
Databáze: | OpenAIRE |
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