Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA257737 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1538880.fastq.gz | Fastqsanger.gz | |||
| SRR1538890.fastq.gz | Fastqsanger.gz | |||
| SRR1538881.fastq.gz | Fastqsanger.gz | |||
| SRR1538891.fastq.gz | Fastqsanger.gz | |||
| SRR1538882.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:The genetic programs that maintain leukemia stem cell (LSC) self-renewal and oncogenic potential have been well defined, however the epigenetic landscape that determines their cellular identity and functionality has not been established. We report that LSCs in MLL-associated leukemia are maintained in an epigenetic state defined by relative genome-wide high-level H3K4me3 methylation and low level H3K79me2. LSC differentiation is associated with dynamic reversal of these broad epigenetic profiles and concomitant down-regulation of the LSC maintenance transcriptional program. LSCs also share with embryonic stem cells a large subset of genes with bivalent histone marks related to embryonic development. The histone demethylase KDM5B negatively regulates MLL-induced leukemogenesis demonstrating the crucial role of the H3K4 global methylome for determining leukemia stem cell fate. Investigation of multiple histone modification marks and RNA Pol II in ckit+ and ckit- cells isolated and fractionated from MLL leukemia mice.
2015-06-26 | E-GEOD-60193 | biostudies-arrayexpress
Project description:Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect. To investigate the effects of Kdm1a KD on histone modifications, we performed chromatin immunoprecipitation followed by next-generation sequencing (ChIP-Seq) in control and Kdm1a KD MLL-AF9 AML cells for dimethyl-H3K4 and dimethyl-H3K9, as well as for trimethyl-H3K4 and trimethyl-H3K9. Dimethyl-H3K4 and dimethyl-H3K9 are targeted for demethylation by KDM1A. For each of these histone modifications, we compared the mean ChIP-Seq signal across and around protein coding genes bound by the MLL-AF9 oncoprotein (Bernt et al., 2011) with the mean signal from genes not bound by MLL-AF9 expressed at high, middle or low levels.
2012-03-28 | E-GEOD-36346 | biostudies-arrayexpress
Project description:The genetic programs that maintain leukemia stem cell (LSC) self-renewal and oncogenic potential have been well defined, however the epigenetic landscape that determines their cellular identity and functionality has not been established. We report that LSCs in MLL-associated leukemia are maintained in an epigenetic state defined by relative genome-wide high-level H3K4me3 methylation and low level H3K79me2. LSC differentiation is associated with dynamic reversal of these broad epigenetic profiles and concomitant down-regulation of the LSC maintenance transcriptional program. LSCs also share with embryonic stem cells a large subset of genes with bivalent histone marks related to embryonic development. The histone demethylase KDM5B negatively regulates MLL-induced leukemogenesis demonstrating the crucial role of the H3K4 global methylome for determining leukemia stem cell fate.
2015-06-26 | GSE60193 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE36346: The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (ChIP-Seq data) GSE36347: The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data) Refer to individual Series
2012-03-28 | E-GEOD-36348 | biostudies-arrayexpress
Project description:The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data)
| PRJNA155567 | ENA
Project description:H3K4 methylation regulates oocyte transcriptome and epigenome
| PRJNA866690 | ENA
Project description:The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (ChIP-Seq data)
| PRJNA155565 | ENA
Project description:Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect.
2012-03-29 | GSE36346 | GEO
Project description:We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by tet-regulated MLL-AF9 co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in Tet-Off MLL-AF9 AML cells in vitro partially phenocopies MLL-AF9 depletion and results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. To compare gene expression changes associated with enforced Id2 expression and MLL-AF9 withdrawal, RNA sequencing analysis was performed on Tet-off MLL-AF9 cells transduced with an Id2 over-expressing or a control vector, or upon MLL-AF9 dox-inducible knock-down.
2016-06-29 | GSE68462 | GEO
Project description:Acute Myeloid Leukemia (AML) with MLL gene rearrangements demonstrate unique gene expression profiles driven by MLL-fusion proteins. Here, we identify the circadian clock transcription factor SHARP1 as a novel oncogenic target in MLL-AF6 AML, which has the worst prognosis among all subtypes of MLL rearranged AMLs. SHARP1 is expressed solely in MLL-AF6 AML, and its expression is regulated directly by MLL-AF6 / DOT1L. Suppression of SHARP1 induces robust apoptosis of human MLL-AF6 AML cells. Genetic deletion in mice delays the development of leukemia and attenuated leukemia-initiating potential, while sparing normal hematopoiesis. Mechanistically, SHARP1 binds to transcriptionally active chromatin across the genome and activates genes critical for cell survival as well as key oncogenic targets of MLL-AF6. Our findings demonstrate the unique oncogenic role for SHARP1 in MLL-AF6 AML.
2018-04-26 | GSE95511 | GEO