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General transcription factor IIB (GTF2B, TFIIB) is a nuclear protein essential for the initiation of transcription by RNA polymerase II, acting as a component of the preinitiation complex (PIC)[1][5]. It binds and stabilizes the TATA-binding protein (TBP)-DNA complex, recruits polymerase II and other factors, and determines the positioning of the transcription start site[1][2]. TFIIB makes sequence-specific protein-DNA contacts at the B recognition element, and interacts with both TBP and the largest subunit of RNA polymerase II (RPB1) through distinct structural domains (zinc ribbon, B reader, B linker, C-terminal core)[1][2]. Its action is crucial for transcription of a subset of cellular genes and nearly all herpesvirus genes, and its acetylation and abundance are regulated in a cell-type- and cell-cycle-dependent manner[3]. Although it is classically considered essential for all mRNA transcription, recent findings suggest that TFIIB is dispensable for many cellular promoters, but remains indispensable for certain viral genes, such as herpes simplex virus[3]. There are no approved drugs directly targeting TFIIB, and broad inhibition could lead to global transcriptomic dysregulation.
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