Nucleosome allostery in pioneer transcription factor binding

Significance Upon binding of effectors, allosteric molecules change their structures and responses to the downstream molecules, which can be viewed as the molecular if−then device. Simulating binding of two pioneer transcription factors (TFs), Sox2 and Oct4, to a nucleosome, which is the fundamental unit of genome folding, we found that a nucleosome acts as a new type of allosteric molecule. Free nucleosomes exhibited rotation-coupled sliding of their DNA among metastable positions. The Sox2 binding on them selected a specific rotational phase of its motif, inducing global sliding of nucleosomal DNA. Consequently, the repositioned DNA affected the accessibility of another TF, Oct4, or the second molecule of Sox2 at a distant region within the nucleosome, which thus is a long-distance allosteric effect.