Probabilistic activation of a typical promoter.

The diagram shows a typical inducible eukaryotic promoter. The basal promoter of the gene contains recognition sequences for abundant nuclear proteins such as Sp1, so that if the gene is in active chromatin, the elements are occupied. The minimal promoter ensures that there is a finite intrinsic low probability of recruitment of TATA-binding protein, and correct assembly an initiation complex including RNA polymerase II (POLII). The cell receives multiple independent signals simultaneously. Some of these may be autocrine, including products of the gene itself. Each signaling pathway increases the frequency with which the distal elements (A-H) are occupied. Each occupied site multiplies the probability of a pulse of transcript so that their effects in combination increase the frequency of transcription exponentially. Activation to a probability of one event per hour would be sufficient to ensure that in each cell at least one allele produces a pulse of transcript within a typical time frame of observation. Assuming absolutely independent regulation of each pathway, failure to activate any one of the cis-acting elements (A-H) would cause at least a 5-fold reduction in mRNA production. At a single-cell level, a probability of 0.2/gene per hour means that only 16% of cells would produce a pulse of the mRNA in a 1-hour time frame (because 4% will produce a second pulse).