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

Cooperative interactions enable low-affinity transcription-factor motifs to significantly influence chromatin accessibility and regulatory potential across the genome.

• Why it matters: Understanding the role of low-affinity motifs is crucial because they are difficult to map and interpret, yet they are key to decoding non-coding genetic variation affecting development, evolution, and disease.
• What they did: Using sequence-to-profile models in mouse embryonic stem cells, the study mapped low-affinity motifs genome-wide and modeled nucleosome-mediated cooperativity through a kinetic approach, revealing their functional dynamics.
• The result: Findings demonstrate that cooperative interactions extend the pioneering range of motifs, enhancing regulatory potential and suggesting low-affinity motifs are widespread in fine-tuning developmental enhancers during evolution.