Deep learning uncovers hidden power of low-affinity motifs.

Low-affinity transcription factor binding sites are functionally important but difficult to map and mechanistically poorly understood. In this issue of Cell Genomics, Weilert et al. leverage sequence-to-function deep learning models to systematically map low-affinity pioneer factor binding sites in mouse embryonic stem cells and reveal how these sites contribute to chromatin opening through soft-syntax nucleosomal cooperativity.