Structures and consequences of pioneer factor binding to nucleosomes

Pioneer transcription factors are able to bind a partially exposed motif on the surface of a nucleosome, enabling the proteins to target sites in silent regions of chromatin that have been compacted by linker histone. The targeting of nucleosomal DNA by pioneer factors has been observed in vitro and in vivo, where binding can promote local nucleosome exposure that allows other transcription factors, nucleosome remodelers, and histone modifiers to engage the chromatin and elicit gene activation or further repression. Pioneer factors thereby establish new gene expression programs during cell fate changes that occur during embryonic development, regeneration, and cancer. Here, we review recent biophysical studies that reveal the structural features and strategies used by pioneer factors to accomplish nucleosome binding and the consequential changes to nucleosomes that can lead to DNA accessibility.