Hierarchical cooperativity mediated by chromatin remodeling; the model of the MMTV transcription regulation

Chromatin remodeling machineries are abundant and diverse in eukaryotic cells but their importance in gene expression remains unclear. Although the influence of nucleosome position on the regulation of gene expression is generally envisioned under the equilibrium perspective, it is proposed that given the ATP-dependence of chromatin remodeling enzymes, certain mechanisms necessitate non-equilibrium treatments. In particular, examination of the celebrated chromatin remodeling system of the mouse mammary tumor virus, in which the binding of transcription factors opens the way to other ones, reveals that breaking equilibrium offers a subtle mode of transcription factor cooperativity, avoids molecular trapping phenomena and allows to reconcile previously conflicting experimental data. The mechanism proposed here provides a control lever of promoter sensitivity and responsiveness, increasing the discernment of gene expression.

► A novel mode of cooperativity between transcription factors is built from experimental observations.
► A role for chromatin remodeling by SWI/SNF ATPases is proposed in the quantitative regulation of gene expression.
► Non-equilibrium treatment allows to reconcile previously conflicting data about the Mouse Mammary Tumor Virus expression.
► This mechanism provides an additional example of the thermodynamic cost of accurate cellular behaviors.