Bromodomain-containing protein 8 (BRD8) Bromodomain 1 (BRD8 BD1)

Bromodomain-containing protein 8 (BRD8) is an epigenetic reader protein and a key component of the NuA4/TIP60 histone acetyltransferase complex (UniProt Q9H0E9; Yamaguchi et al., 2024). It contains two bromodomains, with Bromodomain 1 (BD1) being a critical module for recognizing acetylated lysine residues on histones H4 and H2AZ, as well as non-histone proteins like TWIST1 (Yamaguchi et al., 2024; PMID: 36544021). BRD8 functions as a transcriptional coactivator for several nuclear receptors, including the thyroid hormone receptor and androgen receptor, and plays a significant role in chromatin remodeling and DNA repair (UniProt Q9H0E9; GeneCards). In various cancers, such as glioblastoma and colorectal cancer, BRD8 is often overexpressed and acts as an oncogenic driver by maintaining a repressive chromatin state that sequesters the tumor suppressor p53, thereby preventing the activation of its target genes like p21 (PMID: 36544021; PMID: 38401187). Targeting the BD1 domain with small-molecule inhibitors, such as the chemical probe DN02, has been shown to displace H2AZ, restore p53-mediated growth arrest, and inhibit tumor progression (ProbeChem; PMID: 36544021). Consequently, BRD8 BD1 is an emerging therapeutic target for the treatment of TP53-wild-type malignancies and other epigenetic-driven diseases (PMID: 36544021).

Other names

SMAPSMAP2p120TrCP120Skeletal muscle abundant proteinThyroid hormone receptor coactivating protein of 120 kDaBromodomain-containing protein 8

Inhibition of the bromodomain 1 (BD1) module to disrupt the recognition of acetylated lysine residues on histones (H4, H2AZ) and non-histone proteins (TWIST1), thereby inducing chromatin remodeling and restoring tumor suppressor pathways such as p53-mediated transactivation.