Genomics,Multiomics

Dataset Information

0

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


ABSTRACT: 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.

OTHER RELATED OMICS DATASETS IN: PRJNA315686PRJNA315685PRJNA315563

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE79360 | GEO | 2016/05/01

SECONDARY ACCESSION(S): PRJNA315686

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2016-05-01 | GSE79284 | GEO
2019-11-11 | PXD013245 | Pride
2019-05-02 | GSE129437 | GEO
2023-10-20 | GSE241425 | GEO
2023-10-20 | GSE241424 | GEO
2023-10-20 | GSE241427 | GEO
2024-05-01 | GSE264030 | GEO
2024-05-01 | GSE264008 | GEO
2018-10-18 | PXD010670 | Pride
2018-10-19 | GSE111264 | GEO