Decoding of transcription factor (TF) kinetics by promoters. (A) In simple systems, TF binding directly leads to permissive periods (gray) during which many Pol II are rapidly fired. In this one-to-one model, the TF residence time equals the burst duration. (B) Promoters often integrate complex regulation from multiple TFs and enhancers, as well as the state of chromatin at the promoter, and the kinetics of cluster formation. These interdependent inputs are processed by the transcription machinery, which applies further control layers, leading to multistate bursting dynamics. (PIC) Preinitiation complex.