Transcription initiation factor TFIID subunit 1 bromodomain 2 (TAF1 BD2)

Transcription initiation factor TFIID subunit 1 (TAF1) is the largest component and core scaffold of the TFIID complex, which is essential for the assembly of the pre-initiation complex and the initiation of RNA polymerase II-dependent transcription. The protein contains two tandem bromodomains, with the second bromodomain (BD2) functioning as an epigenetic reader that recognizes acetylated and acylated lysine residues on histone tails. TAF1 BD2 is unique in its ability to bind not only acetyl-lysine but also atypical modifications such as butyryl-lysine and crotonyl-lysine. Dysregulation or mutation of TAF1 is implicated in several diseases, including X-linked dystonia-parkinsonism (XDP), X-linked intellectual disability, and various cancers like acute myeloid leukemia (AML). In oncology, TAF1 supports the activity of oncogenic transcription factors and regulates the p53 tumor suppressor pathway. Small molecule inhibitors such as BAY-299 and GNE-371 have been developed to selectively target TAF1 BD2, often demonstrating synergistic effects when used in combination with BET inhibitors. While TAF1 is a fundamental transcription factor, preclinical evidence suggests that its bromodomains may offer a therapeutic window for targeting cancer cells while sparing normal adult tissues.

Other names

TAFII250 bromodomain 2CCG1 bromodomain 2TAF1(2)TBP-associated factor 250 kDa bromodomain 2Cell cycle gene 1 protein bromodomain 2Transcription initiation factor TFIID 250 kDa subunit bromodomain 2

Inhibition of the TAF1 bromodomain 2 prevents the recognition of acetylated and acylated lysine residues on histones, which disrupts the recruitment of the TFIID complex and other transcriptional machinery to target promoters, thereby modulating gene expression.