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R-2-hydroxyglutarate-mediated inhibition of KDM4A disrupts telomere integrity

ABSTRACT: R-2-hydroxyglutarate-mediated inhibition of KDM4A disrupts telomere integrity

PROVIDER: PRJNA1196302 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31659328.fastq.gz	Fastqsanger.gz
	SRR31659329.fastq.gz	Fastqsanger.gz
	SRR31659330.fastq.gz	Fastqsanger.gz
	SRR31659331.fastq.gz	Fastqsanger.gz
	SRR31659332.fastq.gz	Fastqsanger.gz

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R-2-hydroxyglutarate-mediated inhibition of KDM4A disrupts telomere integrity

Project description:Isocitrate dehydrogenases 1 and 2 are mutated in more than 70% of low-grade glioma. This promotes the production of R-2-hydroxyglutarate (R-2HG) instead of α-ketoglutarate (αKG) and R-2HG will inhibit α-ketoglutarate enzymes like the lysine demethylase KDM4A. We hypothesized that KDM4A inhibition through R-2HG contribute to gliomagenesis. In our study, we showed that KDM4A inhibition leads to telomere defects. By ChIP-seq experiments, we demonstrated that KDM4A localized on telomeric repeats and that its depletion increased the level of H3K9me3 on telomeric chromatin.

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Project description:To establish a robust cellular model system for screening genes associated with cell invasion, we over-expressed the oncogenic translocated promoter region (Tpr)-MET proteins in SCC23 cells (SCC23/MET). Using a functional siRNA screen, we identified that the histone demethylase KDM4A played a critical role in the invasive growth and metastasis of SCC mediated by the Oncogenic MET. To investigate the molecular mechanism through which KDM4A inhibit the tumor cell invasion, we knock-down KDM4A in SCC23/MET cell and performed a gene microarray to examine which genes may be regulaged by kDM4A. We generated two stable cell lines. one was infected with virus containing scramble and another infected with virus infected with virus containing KDM4A shRNA. Total RNA were extracted from these two cell lines and subject to microarray.

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