Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (ChIP-seq)

ABSTRACT: Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (ChIP-seq)

OTHER RELATED OMICS DATASETS IN: GSE79284GSE79360GSE79391

PROVIDER: PRJNA315686 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR3238630.fastq.gz	Fastqsanger.gz
	SRR3238640.fastq.gz	Fastqsanger.gz
	SRR3238631.fastq.gz	Fastqsanger.gz
	SRR3238641.fastq.gz	Fastqsanger.gz
	SRR3238632.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 14

Similar Datasets

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

Project description:Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

| PRJNA315685 | ENA

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (ChIP-seq)

Project description:Our study shows that acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI/SNF chromatin remodeling complex to sustain MYC transcription, rapid cell proliferation, and a block in differentiation. Based on these observations, we derived small-molecule inhibitors of the BRD9 bromodomain, which selectively suppressed the proliferation of mouse and human AML cell lines. To establish these effects as on-target, we engineered a bromodomain-swap allele of BRD9, which retains functionality despite a radically altered bromodomain pocket. Expression of this allele in AML cells conferred resistance to the anti-proliferative effects of our compound series, thus establishing BRD9 as the relevant cellular target. Furthermore, we used an analogous domain-swap strategy to generate an inhibitor-resistant allele of EZH2. Our study provides the first evidence for a role of BRD9 in cancer and reveals a simple genetic strategy for constructing resistance alleles to demonstrate on-target activity of chemical probes in cells.

2016-05-01 | GSE79360 | GEO

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (RNA-seq)

2016-05-01 | GSE79284 | GEO

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (RNA-seq)

Project description:Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (RNA-seq)

| PRJNA315563 | ENA

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition.

Project description:Here we show that acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI-SNF chromatin-remodeling complex to sustain MYC transcription, rapid cell proliferation and a block in differentiation. Based on these observations, we derived small-molecule inhibitors of the BRD9 bromodomain that selectively suppress the proliferation of mouse and human AML cell lines. To establish these effects as on-target, we engineered a bromodomain-swap allele of BRD9 that retains functionality despite a radically altered bromodomain pocket. Expression of this allele in AML cells confers resistance to the antiproliferative effects of our compound series, thus establishing BRD9 as the relevant cellular target. Furthermore, we used an analogous domain-swap strategy to generate an inhibitor-resistant allele of EZH2. To our knowledge, our study provides the first evidence for a role of BRD9 in cancer and reveals a simple genetic strategy for constructing resistance alleles to demonstrate on-target activity of chemical probes in cells.

| S-EPMC4990482 | biostudies-literature

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition

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

2016-05-01 | GSE79391 | GEO

BRD9 regulates leukemic cell survival via STAT5 pathway inhibition

Project description:Leukemia is characterized by genetic and epigenetic mutations resulting in selection of cancer stem cells, which are unable to differentiate. While genetic alterations are difficult to target, the epigenome is intrinsically dynamic and readily offers new therapeutic strategies. Thus, identifying cancer-specific context-dependent targets and unraveling their biological function may open up new therapeutic perspectives. Here, we identify bromodomain-containing protein 9 (BRD9) as a critical target required in acute myeloid leukemia (AML). We show that BRD9 is overexpressed in AML cells including ex vivo primary blasts compared to CD34+. By targeting BRD9 expression in AML, we observed an alteration in proliferation and survival, ultimately resulting in the induction of apoptosis. Intriguingly, genome-wide profiling revealed that BRD9 binds enhancer regions in a cell type-specific manner, regulating cell type-related processes. We unveil a novel BRD9-sustained STAT5 pathway activation via regulation of SOC3 expression levels. Our findings identify a previously undescribed BRD9-STAT5 axis as critical for leukemia maintenance, suggesting BRD9 as a potential therapeutic target.

2019-11-11 | PXD013245 | Pride

Genome-wde mapping of BRD9 binding sites and gene expression changes upon BRD9 knockdown

Project description:Leukemia is characterized by genetic and epigenetic mutations resulting in selection of cancer cells, which are unable to differentiate. While genetic alterations are difficult to target, the epigenome is intrinsically dynamic and readily offers new therapeutic strategies. Thus, identifying cancer-specific context-dependent targets and unraveling their biological function may open up new therapeutic perspectives. Here, we identify bromodomain-containing protein 9 (BRD9) as a critical target required in acute myeloid leukemia (AML). We show that BRD9 is overexpressed in AML cells including ex vivo primary blasts compared to CD34+ cells. By targeting BRD9 expression in AML, we observed an alteration in proliferation and survival, ultimately resulting in the induction of apoptosis. Intriguingly, genome-wide profiling revealed that BRD9 binds enhancer regions in a cell type-specific manner, regulating cell type-related processes. We unveil a novel BRD9-sustained STAT5 pathway activation via regulation of SOCS3 expression levels. Our findings identify a previously undescribed BRD9-STAT5 axis as critical for leukemia maintenance, suggesting BRD9 as a potential therapeutic target.

2019-05-02 | GSE129437 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [scRNA-Seq]

Project description:Chromatin remodeling caused by SWI/SNF (BAF) complexes is essential for regulating cell fates. Of these, BRD9, an essential component of the non-canonical BAF (ncBAF) complex, is post-transcriptionally decayed in multiple types of cancer, especially in myelodysplastic syndrome (MDS). However, how BRD9 loss or ncBAF disruption alters the HSCs' integrity remains unknown. Here, we identify that Brd9 loss enhances chromatin accessibility, promoting myeloid-lineage skewing at the expense of B cell development in vivo, followed by MDS development. Brd9 significantly colocalizes with Ctcf, whose peaks are stoichiometrically enhanced by Brd9 loss, leading to increased chromatin loops with the larger chromatin domains intact. These Ctcf-associated chromatin loops newly occur in myeloid-related genes. These data uncover the unrecognized roles of BRD9/ncBAF in the cell fate specification of HSCs via fine-tuning chromatin loops and shed light on the mechanism of ncBAF-disrupted cancer.

2023-10-31 | GSE203321 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [mouse_Brd9_ATAC-seq]

2023-10-31 | GSE236329 | GEO