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TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE136283 | GEO | 2021/02/08

REPOSITORIES: GEO

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TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion [RNA-seq]

Project description:we conducted RNA sequencing using human cerebral organoids treated with TAT peptides. Each group with one replicates.

2021-02-08 | GSE136282 | GEO

TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion [ChIP-seq]

Project description:we conducted chromotin Immunoprecipitation sequencing (ChIP-seq) using human cerebral organoids treated with TAT-Scrambled (Short for TAT-Scr) with the sequence of YGRKKRRQRRR-FRVRYWFQGCHSEDPWR and TAT-465-481, a special peoptide designed for inhibition of TBC1D3, with the sequence of YGRKKRRQRRR-EGPWFRHYDFRQSCWVR.

2021-02-08 | GSE136281 | GEO

TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion

Project description:TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion

| PRJNA561829 | ENA

TBC1D3 Associates with the Histone Lysine N-methyltransferase G9a to Affect the Promotion of Neural Progenitors and Cortical Expansion in an Epigenetic Way

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-12-01 | GSE131254 | GEO

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

Project description: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.

| S-EPMC7810367 | biostudies-literature

TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion [ChIP-seq]

Project description:TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion [ChIP-seq]

| PRJNA561832 | ENA

TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion [RNA-seq]

Project description:TBC1D3 suppression of the Histone Lysine N-methyltransferase G9a promotes the generation of neural progenitors and cortical expansion [RNA-seq]

| PRJNA561831 | ENA

TBC1D3 Associates with the Histone Lysine N-methyltransferase G9a to Affect the Promotion of Neural Progenitors and Cortical Expansion in an Epigenetic Way [RNA-Seq]

Project description:we conducted RNA sequencing using human cerebral organoids treated with TAT peptides

2021-12-01 | GSE131250 | GEO

TBC1D3 Associates with the Histone Lysine N-methyltransferase G9a to Affect the Promotion of Neural Progenitors and Cortical Expansion in an Epigenetic Way [ChIP-Seq]

Project description:we conducted chromotin Immunoprecipitation sequencing (ChIP-seq) using mouse cortical tissues from TBC1D3-transgenic mice and wild-typed mice

2021-12-01 | GSE131080 | GEO

The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice.

Project description:Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding.

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