Dissociation rate compensation mechanism for budding yeast pioneer transcription factors.

Benjamin T Donovan, Hengye Chen, Caroline Jipa, Lu Bai, Michael G Poirier
Author Information
  1. Benjamin T Donovan: Biophysics Graduate Program, The Ohio State University, Columbus, United States. ORCID
  2. Hengye Chen: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, State College, United States.
  3. Caroline Jipa: Department of Physics, The Ohio State University, Columbus, United States.
  4. Lu Bai: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, State College, United States. ORCID
  5. Michael G Poirier: Biophysics Graduate Program, The Ohio State University, Columbus, United States. ORCID

Abstract

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.

Keywords

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Grants

  1. 1516979/National Science Foundation
  2. R01 GM121858/NIGMS NIH HHS
  3. R01 GM121966/NIH HHS
  4. T32 GM086252/NIH HHS
  5. R01 GM121966/NIGMS NIH HHS

MeSH Term

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
DNA, Fungal
DNA-Binding Proteins
Histones
Nucleosomes
Protein Binding
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription Factors

Chemicals

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
CBF1 protein, S cerevisiae
DNA, Fungal
DNA-Binding Proteins
Histones
Nucleosomes
REB1 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Transcription Factors

Word Cloud

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