Bromodomain-containing protein 2 (BRD2) first bromodomain (BD1) (BRD2 BD1)

Bromodomain-containing protein 2 (BRD2) is a member of the Bromodomain and Extra-Terminal (BET) family of epigenetic readers [1.1.1, 1.5.2]. The first bromodomain (BD1) of BRD2 is one of two tandem domains that specifically recognize and bind to acetylated lysine residues on histone tails, particularly histone H4 [1.1.1, 1.4.1]. This binding facilitates the recruitment of transcriptional machinery, such as the E2F transcription factor and RNA polymerase II, to regulate the expression of genes involved in the cell cycle and pro-inflammatory responses [1.1.2, 1.5.1]. In many diseases, particularly cancers like leukemia and lymphoma, BRD2 BD1 is involved in maintaining oncogenic transcriptional programs, including the expression of MYC [1.1.3, 1.5.1]. Pharmacological targeting of BRD2 BD1 with small-molecule inhibitors, such as JQ1 or selective BD1 inhibitors like Olinone, works by competitively occupying the acetyl-lysine binding pocket [1.1.1, 1.3.1]. This displacement of BRD2 from chromatin leads to the downregulation of target genes and has shown therapeutic potential in treating malignancies and inflammatory disorders [1.2.1, 1.4.1]. However, clinical use of BET inhibitors is often limited by safety concerns such as thrombocytopenia and gastrointestinal toxicity [1.3.3, 1.3.4].

Other names

RING3RNF3D6S113EBromodomain-containing protein 2BRD2Female sterile homeotic-related gene 1BRD2 BD1 bromodomain

Competitive inhibition of acetyl-lysine binding to the bromodomain pocket, leading to displacement from chromatin and suppression of gene transcription [1.1.1, 1.3.4].