Dissociation rate compensation mechanism for budding yeast pioneer transcription factors

• Published in: eLife Vol. 8
• Main Authors: Donovan, Benjamin T, Chen, Hengye, Jipa, Caroline, Bai, Lu, Poirier, Michael G
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 19.03.2019; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; binding and dissociation kinetics; Binding sites; Biochemistry; Chromosomes and Gene Expression; Deoxyribonucleic acid; DNA; DNA binding proteins; DNA, Fungal - metabolism; DNA-Binding Proteins - metabolism; Experiments; Genomes; Glycerol; Histones - metabolism; Medical research; Migration; Nucleosomes; Nucleosomes - metabolism; Occupancy; Physiological aspects; pioneer factors; Protein Binding; Proteins; Reb1; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; single molecule; Structural Biology and Molecular Biophysics; Time series; Transcription factors; Transcription Factors - metabolism; United States; United States > US; Ohio; Pennsylvania; single molecule; Reb1; nucleosomes; chromosomes; pioneer factors; structural biology; binding and dissociation kinetics; molecular biophysics; gene expression; S. cerevisiae
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.43008

Nucleosomes restrict the occupancy of most transcription factors (TF) by reducing binding and accelerating dissociation, while a small group of TFs have high affinities to nucleosome-embedded sites and facilitate nucleosome displacement. To understand this process mechanistically, we investigated two TFs, Reb1 and Cbf1. We show that these factors bind to their sites within nucleosomes with similar binding affinities as to naked DNA, trapping a partially unwrapped nucleosome without histone eviction. Both the binding and dissociation rates of Reb1 and Cbf1 are significantly slower at the nucleosomal sites relative to those for naked DNA, demonstrating that the high affinities are achieved by increasing the dwell time on nucleosomes in order to compensate for reduced binding. Reb1 also shows slow migration rate in the yeast nuclei. These properties are similar to those of human pioneer factors (PFs), suggesting that the mechanism of nucleosome targeting is conserved from yeast to humans.