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Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE156821 | GEO | 2020/08/25

REPOSITORIES: GEO

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Brd4-bound enhancers drive cell-intrinsic sex differences in glioblastoma.

Project description:Sex can be an important determinant of cancer phenotype, and exploring sex-biased tumor biology holds promise for identifying novel therapeutic targets and new approaches to cancer treatment. In an established isogenic murine model of glioblastoma (GBM), we discovered correlated transcriptome-wide sex differences in gene expression, H3K27ac marks, large Brd4-bound enhancer usage, and Brd4 localization to Myc and p53 genomic binding sites. These sex-biased gene expression patterns were also evident in human glioblastoma stem cells (GSCs). These observations led us to hypothesize that Brd4-bound enhancers might underlie sex differences in stem cell function and tumorigenicity in GBM. We found that male and female GBM cells exhibited sex-specific responses to pharmacological or genetic inhibition of Brd4. Brd4 knockdown or pharmacologic inhibition decreased male GBM cell clonogenicity and in vivo tumorigenesis while increasing both in female GBM cells. These results were validated in male and female patient-derived GBM cell lines. Furthermore, analysis of the Cancer Therapeutic Response Portal of human GBM samples segregated by sex revealed that male GBM cells are significantly more sensitive to BET (bromodomain and extraterminal) inhibitors than are female cells. Thus, Brd4 activity is revealed to drive sex differences in stem cell and tumorigenic phenotypes, which can be abrogated by sex-specific responses to BET inhibition. This has important implications for the clinical evaluation and use of BET inhibitors.

| S-EPMC8072233 | biostudies-literature

Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma.

Project description:We report the application of Calling Card sequencing technology for high-throughput profiling of Brd4-bound enhancers in male and female mouse glioblastoma.

2020-08-23 | GSE156678 | GEO

Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma [ChIP-Seq]

Project description:We report the application of ChIP-seq for high-throughput profiling of histone mark H3K27ac in male and female mouse glioblastoma.

2020-08-26 | GSE156820 | GEO

Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma [RNA-Seq]

Project description:We report the application of RNA-seq for high-throughput profiling of transcriptom in male and female mouse glioblastoma.

2020-08-26 | GSE156819 | GEO

Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma

Project description:Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma

| PRJNA659250 | ENA

Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma.

Project description:Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma.

| PRJNA658688 | ENA

Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma [ChIP-Seq]

Project description:Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma [ChIP-Seq]

| PRJNA659378 | ENA

Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma [RNA-Seq]

Project description:Brd4-bound enhancers drive cell intrinsic sex differences in glioblastoma [RNA-Seq]

| PRJNA659257 | ENA

NF-kB coordinates rapid, BRD4-dependent remodeling of proinflammatory super-enhancers

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-09-29 | E-GEOD-54000 | biostudies-arrayexpress

Regulatory Sharing Between Estrogen Receptor α Bound Enhancers

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

2020-03-18 | GSE147142 | GEO

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