Cooperativity enables widespread role of low-affinity motifs in chromatin accessibility and increases regulatory potential.

Low-affinity transcription-factor motifs significantly influence chromatin accessibility by cooperating through intra-nucleosomal soft syntax, expanding regulatory potential in mouse embryonic stem cells.

• Why it matters: Understanding the role of low-affinity motifs is crucial because they are difficult to map and their mechanistic functions are not well understood, limiting insights into development, evolution, and disease.
• What they did: The study used sequence-to-profile models to reliably map low-affinity motifs across the genome and developed a kinetic model to demonstrate how nucleosome-mediated cooperativity enhances their pioneering range.
• The result: Findings reveal that low-affinity motifs, through pioneer cooperativity, operate at higher ranges across varying TF concentrations, increasing regulatory potential and shaping developmental enhancers.