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Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [ChIP-seq]

ABSTRACT: Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [ChIP-seq]

PROVIDER: PRJNA515968 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8460390.fastq.gz	Fastqsanger.gz
	SRR8460391.fastq.gz	Fastqsanger.gz
	SRR8460392.fastq.gz	Fastqsanger.gz
	SRR8460393.fastq.gz	Fastqsanger.gz
	SRR8460394.fastq.gz	Fastqsanger.gz

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Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia

Project description:Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia

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Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [ChIP-seq]

Project description:In this study we identified the histone demethylase KDM4A as an essential and selective regulator of AML oncogenic potential. ChIPseq was used to identify KDM4A bound genes and follow changes in H3K9me2/3 and H3K27me3 following KDM4A knockdown in MLL-AF9 human AML THP-1 cells

2021-01-17 | GSE125375 | GEO

Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [RNA-seq]

Project description:Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [RNA-seq]

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Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia [RNA-seq]

Project description:In this study we identified the histone demethylase KDM4A as an essential and selective regulator of AML oncogenic potential. RNAseq was used to follow the changes in gene expression following KDM4A knockdown in MLL-AF9 human AML THP-1 cells

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Histone demethylase KDM4A-mediated promotion of PAF1/NFATC2 expression is required for oncogenesis in MLL-AF9 acute myeloid leukemia

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

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Determining the DNA-binding targets of NFATc2 in the AML cell line THP-1

Project description:Based on previous work on the KDM histone demethylase family in AML, the transcription factor NFATC2 was identified as a regulatory target of KDM4A in MLL-AF9-rearrangement THP-1 cells. Our existing work examined the elements of the transcriptome regulated by NFATC2 in THP-1 cells and so, to further this work, we aimed to characterise the DNA-binding targets of NFATc2 in these cells. In this study, we used NFATc2 immunoprecipitation for ChIP-seq in untreated THP-1 cells, in order to determine these.

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Project description:We previously identified an essential role for the H3K9me3 histone demethylase, KDM4A, in maintaining AML cell survival, with genetic depletion by shRNA of KDM4A inducing leukaemic cell death with little effect on normal haematopoiesis. We hypothesised KDM4A inhibition may represent a novel and effective strategy to treat AML. To address this, we provided proof-of-principle for the use of KDM4 inhibitors (KDM4Ai) and fully characterised their functional potential in AML cells and identified the epigenetic mechanisms underpinning the essential role of KDM4A activity in THP-1 cells using both ChIP-seq and RNA-seq, delineating and functionally validating the epigenomic network regulated by KDM4A, showing that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing down-regulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C.

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