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BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE158551 | GEO | 2022/09/15

REPOSITORIES: GEO

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BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network.

Project description:Inhibition of the tumour suppressive function of p53 (encoded by TP53) is paramount for cancer development in humans. However, p53 remains unmutated in the majority of cases of glioblastoma (GBM)-the most common and deadly adult brain malignancy1,2. Thus, how p53-mediated tumour suppression is countered in TP53 wild-type (TP53WT) GBM is unknown. Here we describe a GBM-specific epigenetic mechanism in which the chromatin regulator bromodomain-containing protein 8 (BRD8) maintains H2AZ occupancy at p53 target loci through the EP400 histone acetyltransferase complex. This mechanism causes a repressive chromatin state that prevents transactivation by p53 and sustains proliferation. Notably, targeting the bromodomain of BRD8 displaces H2AZ, enhances chromatin accessibility and engages p53 transactivation. This in turn enforces cell cycle arrest and tumour suppression in TP53WT GBM. In line with these findings, BRD8 is highly expressed with H2AZ in proliferating single cells of patient-derived GBM, and is inversely correlated with CDKN1A, a canonical p53 target that encodes p21 (refs. 3,4). This work identifies BRD8 as a selective epigenetic vulnerability for a malignancy for which treatment has not improved for decades. Moreover, targeting the bromodomain of BRD8 may be a promising therapeutic strategy for patients with TP53WT GBM.

| S-EPMC10189659 | biostudies-literature

BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [ATAC-seq]

Project description:Chromatin accessibility profiling by high throughput sequencing

2022-09-16 | GSE199364 | GEO

BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [RNA-seq]

Project description:Transcriptome analysis by high throughput sequencing

2022-09-16 | GSE158550 | GEO

BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [ChIP-seq]

Project description:Genome-wide binding/occupancy profiling by high throughput sequencing

2022-09-16 | GSE158549 | GEO

BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network

Project description:BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network

| PRJNA665550 | ENA

BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [ATAC-seq]

Project description:BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [ATAC-seq]

| PRJNA819459 | ENA

BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [ChIP-seq]

Project description:BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [ChIP-seq]

| PRJNA665554 | ENA

BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [RNA-seq]

Project description:BRD8 maintains glioblastoma by epigenetic reprogramming of the P53 network [RNA-seq]

| PRJNA665555 | ENA

ZFP708 maintains DNA methylation during epigenetic reprogramming in embryos

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

2019-03-27 | GSE126688 | GEO

The Bromodomain Containing 8 (BRD8) Transcriptional Network in Human Lung Epithelial Cells

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

2021-01-29 | GSE158688 | GEO

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