Variation in gene expression is an essential material for biological diversity among single cells^{1, 2, 3}, individuals^{4, 5, 6} and populations or species^{7, 8, 9}. Here we show that expression variability is an intrinsic property that persists at those different levels. Each promoter seems to have a unique capacity to respond to external signals that can be environmental, genetic or even stochastic. Our investigation into nucleosome organization of variably responding promoters revealed a commonly positioned nucleosome at a critical regulatory region where most transcription start sites and TATA elements are located, a deviation from typical nucleosome-free status. The nucleotide sequences in this region of variable promoters showed a high propensity for DNA bending and a periodic distribution of particular dinucleotides, encoding preferences for DNA–nucleosome interaction. Variable expression is likely to occur during removal of this nucleosome for gene activation. This is a unique example of how promoter sequences intrinsically encode regulatory flexibility, which is vital for biological processes such as adaptation, development and evolution.

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