Figure 7.

Steric model of Gdown1 repression and relief by Mediator. In this model, Mediator acts as a scaffold to promote the association of RNAPII with TFIIF to create an unfavourable circumstance for Gdown1 to dwell on RNAPII at the overlapping sites of TFIIF; henceforth destabilizing the association between RNAPII and Gdown1 and eventually yielding the swapping between Gdown1 and TFIIF on RNAPII to allow for transcription initiation to ensue (RNAPII is coloured in cyan, Gdown1 in green, TFIIF in blue, and Mediator in grey. PIC stands for ‘pre-initiation complex’). (A) When RNAPII(G) is recruited to the promoter, the PIC would not be generated considering the exclusion of TFIIF on RNAPII and transcription would be prevented. (B) Steric hindrance of TFIIF binding to RNAPII by Gdown1 is relieved by the Mediator complex and Mediator swaps TFIIF for Gdown1 on RNAPII. (C) Once Gdown1 is removed, promoter escape ensues with the possibility of some RNAPII enzymes to re-associate with Gdown1, in accord with recent findings of RNAPII(G) downstream of promoters (Cheng et al, 2012) and others to remain with TFIIF. Considering that RNAPII(G) is substoichiometric, it is also possible that RNAPII initiates at promoters in the absence of Gdown1 and therefore unhindered by Gdown1.