Abstract

Chromatin dynamics are mediated by remodeling enzymes and play crucial roles in gene regulation, as established in a paradigmatic model, the Saccharomyces cerevisiae PHO5 promoter. However, effective nucleosome dynamics, that is, trajectories of promoter nucleosome configurations, remain elusive. Here, we infer such dynamics from the integration of published single-molecule data capturing multi-nucleosome configurations for repressed to fully active PHO5 promoter states with other existing histone turnover and new chromatin accessibility data. We devised and systematically investigated a new class of 'regulated on-off-slide' models simulating global and local nucleosome (dis)assembly and sliding. Only seven of 68,145 models agreed well with all data. All seven models involve sliding and the known central role of the N-2 nucleosome, but regulate promoter state transitions by modulating just one assembly rather than disassembly process. This is consistent with but challenges common interpretations of previous observations at the PHO5 promoter and suggests chromatin opening by binding competition.

Highlights

  • Eukaryotic DNA is packaged inside the nucleus with several layers of compaction

  • After systematic analysis of all possible regulated on-off-slide models up to a fixed number of fitted parameters, we found only very few models in agreement with all four data sets and were able to describe the effective dynamics of nucleosome configurations during chromatin remodeling at the PHO5 promoter in yeast

  • PHO5 promoter nucleosome dynamics can be viewed in two different levels of detail

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Summary

Introduction

Eukaryotic DNA is packaged inside the nucleus with several layers of compaction. The most basic layer consists of nucleosomes, where of DNA are wrapped around a histone protein octamer (Luger et al, 1997). Nucleosomes occupy most of the genome and hinder binding of other proteins to DNA, for example transcription factors (Venter et al, 1994; Bell et al, 2011; Lai and Pugh, 2017), replication machinery (Chang et al, 2016) and DNA repair enzymes (Hauer and Gasser, 2017). This hindrance can be overcome by chromatin remodeling enzymes. To decipher the resulting nucleosome dynamics, detailed measurements of both, steady state and dynamic quantities are key

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