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CDK9 inhibition with AZD4573 in DLBCL

ABSTRACT: We report the effects of CDK9 inhibition (AZD4573) on the epigenetic landscape in Diffuse Large B-cell Lymphoma (DLBCL). This study utilized the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess genome-wide chromatin accessibility in two DLBCL cell lines, OCI-LY3 and VAL, treated with AZD4573 (30 nM) at 0, 3, and 8 hours. We found that CDK9 inhibition led to gain and loss of accessible chromatin genome-wide, with enrichment of CTCF/BORIS motifs in decreased accesibility regions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198851 | GEO | 2022/03/21

REPOSITORIES: GEO

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CDK9 inhibition with AZD4573 in DLBCL

Project description:We report the effects of CDK9 inhibition (AZD4573) on the epigenetic landscape in Diffuse Large B-cell Lymphoma (DLBCL). This study utilized chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) to assess genome-wide post-translational histone modifications (H3K27ac and H3K4me3) and DNA occupancy of transcriptional proteins (RNAPII and BRD4) in two DLBCL cell lines, OCI-LY3 and VAL, treated with the CDK9 inhibitor AZD4573 (30 nM). Cells were treated for 0, 3 and 8 hours prior to harvest. After 8-hour exposure, drug was washed out and cells were harvested after 24 hours. We found that CDK9 inhibition led to an increase in RNAPII promoter proximal pausing, and increase in BRD4 enrichment on the promoter, and a decrease in promoter H3K4me3. Treatment induced reprograming of the super-enhancer landscape including loss of super-enhancers next to genes in oncogenic pathways.

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CDK9 inhibition with AZD4573 in DLBCL

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AZD4573 is a highly selective CDK9 inhibitor that suppresses Mcl-1 and induces apoptosis in hematological cancer cells

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RNA-seq data corresponding to: AZD4573 is a highly selective CDK9 inhibitor that suppresses Mcl-1 and induces apoptosis in hematological cancer cells

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