Bromodomain-containing protein 8 (BRD8) bromodomain 2 (BRD8 BD2)

Bromodomain-containing protein 8 (BRD8) is a critical regulatory subunit of the NuA4 histone acetyltransferase (HAT) complex, which is essential for transcriptional activation and DNA damage repair (UniProt Q9H0E9). The protein contains two distinct bromodomains, with the second bromodomain (BD2) functioning as an epigenetic reader that specifically recognizes and binds to acetylated lysine residues on histone tails, particularly histone H4 (PubMed: 22464331). This binding facilitates the recruitment of the NuA4 complex to specific gene promoters, promoting an open chromatin state and active transcription. In oncology, BRD8 is frequently overexpressed and has been implicated in the progression of various malignancies, including prostate and colorectal cancers, where it often modulates androgen receptor signaling or suppresses p53-mediated apoptotic pathways (PubMed: 26365766). Targeting the BD2 domain with small molecule inhibitors represents a promising therapeutic strategy to disrupt these aberrant gene expression patterns in cancer cells (PubMed: 30204038). Unlike the more widely studied BET family bromodomains, BRD8 BD2 possesses unique structural features that may allow for the development of highly selective inhibitors with reduced systemic toxicity.

Other names

p120SMAPSMAP2Skeletal muscle-abundant proteinBromodomain-containing protein 8

Competitive inhibition of the bromodomain's binding to acetylated lysine residues on histone tails, thereby disrupting the recruitment of the NuA4 histone acetyltransferase complex to chromatin.