Figure 1.

Transcription initiation complex assembly. (a) TFIID complex. TFIID is organized into three lobes: lobes A, B and C (TFIID-A, -B and -C). Certain TAFs are present in both lobes A and B and several heterodimerize through their histone-folding domains (HFDs). The cryo-electron microscopy (cryoEM)-visible parts of TAF1 locate/within TFIID-C i.e. within the C lobe. (b) TFIID exists in two major conformations: ‘canonical’ or ‘promoter-bound’ TFIID. Canonical TFIID exists in a relatively compact conformation, whereas promoter-bound TFIID binds to the TATA box via TBP together with TFIIA, stabilizing the complex at the core promoter. Aside from the TATA box, eukaryotic core promoters comprise multiple elements including initiator (INR), motive ten element (MTE) and downstream core promoter element (DPE) [11]; for (c) and (d), only the TATA box is shown for simplicity. TFIID structure and conformational changes are based on cryoEM data [10,12] and are described in Malik & Roeder [13]. (c) Pre-initiation complex (PIC) assembly. TFIID recognizes the core promoter of a gene to be transcribed, with TBP and TFIIA, then further recruits TFIIB, RNA polymerase II (pol II), TFIIF, TFIIH and TFIIE to assemble the PIC. (d) Mediator-bound PIC. Basal (a.k.a. general) transcription factors, pol II, and the coactivator mediator are recruited to the PIC [11]. Mediator facilitates interactions between the TFIID and transcriptional activators. Current models are reviewed in detail in Malik & Roeder [13]. Size of DNA and proteins not to scale. TAF, TBP-associated factor; TBP, TATA box-binding protein; (TF)IIA, B, D, E, F, H, basal transcription factor 2A, B, D, E, F, H. Created with BioRender.com.