Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells

Federico Comoglio, Marta Simonatto, Sara Polletti, Xin Liu, Stephen T Smale, Iros Barozzi, Gioacchino Natoli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1159-1174
Number of pages16
JournalGenes and Development
Volume33
Issue number17-18
DOIs
Publication statusPublished - Sep 1 2019

Keywords

  • 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

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  • Cite this

    Comoglio, F., Simonatto, M., Polletti, S., Liu, X., Smale, S. T., Barozzi, I., & Natoli, G. (2019). Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells. Genes and Development, 33(17-18), 1159-1174. https://doi.org/10.1101/gad.326348.119