Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

Genes Dev. 2019 Sep 1;33(17-18):1159-1174. doi: 10.1101/gad.326348.119. Epub 2019 Aug 1.

Abstract

Accessibility of the genomic regulatory information is largely controlled by the nucleosome-organizing activity of transcription factors (TFs). While stimulus-induced TFs bind to genomic regions that are maintained accessible by lineage-determining TFs, they also increase accessibility of thousands of cis-regulatory elements. Nucleosome remodeling events underlying such changes and their interplay with basal positioning are unknown. Here, we devised a novel quantitative framework discriminating different types of nucleosome remodeling events in micrococcal nuclease ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) data sets and used it to analyze nucleosome dynamics at stimulus-regulated cis-regulatory elements. At enhancers, remodeling preferentially affected poorly positioned nucleosomes while sparing well-positioned nucleosomes flanking the enhancer core, indicating that inducible TFs do not suffice to overrule basal nucleosomal organization maintained by lineage-determining TFs. Remodeling events appeared to be combinatorially driven by multiple TFs, with distinct TFs showing, however, different remodeling efficiencies. Overall, these data provide a systematic view of the impact of stimulation on nucleosome organization and genome accessibility in mammalian cells.

Keywords: chromatin; macrophages; nucleosome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromatin Immunoprecipitation
  • High-Throughput Nucleotide Sequencing
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Micrococcal Nuclease / metabolism
  • Nucleosomes / metabolism*
  • Regulatory Elements, Transcriptional / physiology*
  • Transcription Factors / metabolism*

Substances

  • Nucleosomes
  • Transcription Factors
  • Micrococcal Nuclease