BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network.

ABSTRACT: 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 malignancy^1,2. Thus, how p53-mediated tumour suppression is countered in TP53 wild-type (TP53^WT) 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

SUBMITTER: Sun X 

PROVIDER: S-EPMC10189659 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature