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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: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE125375 | GEO | 2021/01/17

REPOSITORIES: GEO

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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

2021-01-17 | GSE125374 | GEO

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

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

2021-01-17 | GSE125376 | GEO

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

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

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Identification of Kdm4a and c target genes in MLL-AF9 transformed mouse GMPs (L-GMP) [ChIP-seq]

Project description:In this study we identify genes, that are bound by Kdm4a and Kdm4c in L-GMP cells. MLL-AF9 transformed L-GMP cell lines conditional knockout for Kdm4a, b and c, were derived from leukemic mice. The cells were treated with 4-hydroxytamoxifen and chromatin was prepared from untreated cells (Ctrl) and cells treated for 96hr.

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Project description:In this study we identify genes, that are deregulated in Kdm4a, b and c triple knockout L-GMP cells compared WT L-GMP cells. Four MLL-AF9 transformed L-GMP cell lines conditional knockout for Kdm4a, b and c, were derived from leukemic mice. The cells were treated with 4-hydroxytamoxifen and total RNA was prepared from 0h, 48h and 96h time points.

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Efficient Elimination of Acute Myeloid Leukaemia Cells through Inhibition of KDM4A

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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Project description:Purpose: We performed RNA-Seq on 2.5dpc mouse hypothalamus, pituitary, ovary and uterus of 8-10 week old littermate female control and Kdm4a knockout mice. Upon observing for the extent of altered genes of physiological relevance to observed female infertility phenotype, this would help us narrow down the most relevant tissue to perform genome wide ChipSeq binding profiles for Kdm4a, H3K4me3 and H3K9me3. This dataset would present likely target genes under direct control of Kdm4a.

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