Promoter architecture associated with expression flexibility [46–48]. Top: the architecture of a typical promoter in which nucleosomes are regularly positioned but are excluded from a particular region upstream of the transcription start site. This nucleosome-free region (NFR) contains accessible binding sites for (few) transcriptional regulators (TF). Bottom: the architecture of promoters with high expression flexibility. These promoters tend to have a TATA box and multiple other binding sites for transcriptional regulators. Nucleosome positions are more dynamic (double-headed arrows) and nucleosomes are not strongly excluded from any particular region, and therefore compete with transcriptional regulators at their binding sites. These promoters are thus dependent on the activity of multiple transcriptional regulators and chromatin regulators (CR), which increases their mutational target size.