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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]

ABSTRACT: 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]

PROVIDER: PRJNA542629 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9047560.fastq.gz	Fastqsanger.gz
	SRR9047557.fastq.gz	Fastqsanger.gz
	SRR9047558.fastq.gz	Fastqsanger.gz
	SRR9047559.fastq.gz	Fastqsanger.gz

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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

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

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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: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]

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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.

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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

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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.

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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

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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.

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Change in transcriptome upon G9a knockdown in RD ERMS (Embryonal Rhabdomyosarcoma) cells

Project description:The Wnt signaling pathway is down-regulated in embryonal rhabdomyosarcoma (ERMS) and contributes to the block of myogenic differentiation. Epigenetic mechanisms leading to its suppression are unknown and could pave the way towards novel therapeutic modalities. In this study, we demonstrate that the lysine methyltransferase G9a suppresses the canonical Wnt signalling pathway by activating expression of the Wnt antagonist DKK1. Inhibition of G9a expression or activity reduced DKK1 expression and elevated canonical Wnt signalling resulting in myogenic differentiation in vitro and in vivo. Mechanistically, G9a impacted Sp1 and p300 enrichment at the DKK1 promoter in a methylation-dependent manner. The reduced tumor growth upon G9a deficiency was reversed by recombinant DKK1 or LGK974, which also inhibits Wnt signaling. Consistently, among thirteen drugs targeting chromatin modifiers, G9a inhibitors were highly effective in reducing ERMS cell viability. Together, our study demonstrates that ERMS cells are vulnerable to G9a inhibitors and suggest that targeting the G9a-DKK1--catenin node holds promise for differentiation therapy.

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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]

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