Gene definition model. (A) In the absence of transcription, the DNA forms nucleosomes except where prevented by bound TFs (such as the GRFs) or by the DNA structure. (B) Transcription begins indiscriminately from nucleosome-free regions in proportion to the efficiency of pre-initiation complex (PIC) formation. Promoters compete with one another in cis through the act of transcription. (C) An equilibrium is reached where some promoters are active and others are repressed. Successful cleavage and polyadenylation reinforces the promoter choice. (D) If a nucleosome-free region is destroyed (for instance, through loss of GRF binding), it is no longer competent for initiating transcription. Downstream promoters are then de-repressed, become active, and a new equilibrium is reached.
