Figure 8. Molecular and mechanistic model for how the TBS in a promoter can lead to different TBP assemblies in a population of cells and thereby lead to noise in gene expression levels.

(a) The TBS within a gene's promoter in a cell population can harbour different TBP assemblies following a given path through a chain of events/decision tree (top). A promoter can harbour a number of possible microstates: free (f), TFIID (D), TBP (T), SAGA (S) or Mot1p (M). Depending on the assembled TBP complex, the promoter will either be transcriptionally active or silent. The extent of switching between transcriptionally permissive or non-permissive states either (i) over time in an individual (time-average) or (ii) at an instance between individual cells in a population (space-average) determines the extent of expression noise (bottom). (b) TBS type determines the TBP complexes that can be assembled and thus can explain the emergence of noise. A TATA-box TBS can host a larger variety of microstates with different transcriptional output (top-right), which leads to more variability in gene expression levels between individual cells in a population. TATA-like TBS predominantly end up in the TFIID microstate, which leads to consistent expression output (top-left) and less variability in expression levels between individual cells in a population. In a population of cells, the different individuals might switch between the different TBP assemblies at a promoter and this will manifest as differences in the expression level of a gene (dark yellow for low abundance and light yellow for high abundance).