Systematic Study of Nucleosome-Displacing Factors in Budding Yeast

Nucleosomes present a barrier for the binding of most transcription factors (TFs). However, special TFs known as nucleosome-displacing factors (NDFs) can access embedded sites and cause the depletion of the local nucleosomes as well as repositioning of the neighboring nucleosomes. Here, we developed a novel high-throughput method in yeast to identify NDFs among 104 TFs and systematically characterized the impact of orientation, affinity, location, and copy number of their binding motifs on the nucleosome occupancy. Using this assay, we identified 29 NDF motifs and divided the nuclear TFs into three groups with strong, weak, and no nucleosome-displacing activities. Further studies revealed that tight DNA binding is the key property that underlies NDF activity, and the NDFs may partially rely on the DNA replication to compete with nucleosome. Overall, our study presents a framework to functionally characterize NDFs and elucidate the mechanism of nucleosome invasion. Nucleosome-displacing factors (NDFs) open chromosomes and allow transcription factors to bind and initiate gene expression. Yan et al. developed a high-throughput method to identify NDFs and study their activities. Comparison between NDFs and other factors with no NDF activities generates insights into the mechanism of nucleosome invasion.