Insights into Nucleosome Organization in Mouse Embryonic Stem Cells through Chemical Mapping

Lilien N. Voong, Liqun Xi, Amy C. Sebeson, Bin Xiong, Jiping Wang*, Xiaozhong Wang

*Corresponding author for this work

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Nucleosome organization influences gene activity by controlling DNA accessibility to transcription machinery. Here, we develop a chemical biology approach to determine mammalian nucleosome positions genome-wide. We uncovered surprising features of nucleosome organization in mouse embryonic stem cells. In contrast to the prevailing model, we observe that for nearly all mouse genes, a class of fragile nucleosomes occupies previously designated nucleosome-depleted regions around transcription start sites and transcription termination sites. We show that nucleosomes occupy DNA targets for a subset of DNA-binding proteins, including CCCTC-binding factor (CTCF) and pluripotency factors. Furthermore, we provide evidence that promoter-proximal nucleosomes, with the +1 nucleosome in particular, contribute to the pausing of RNA polymerase II. Lastly, we find a characteristic preference for nucleosomes at exon-intron junctions. Taken together, we establish an accurate method for defining the nucleosome landscape and provide a valuable resource for studying nucleosome-mediated gene regulation in mammalian cells.

Original languageEnglish (US)
Pages (from-to)1555-1570.e15
JournalCell
Volume167
Issue number6
DOIs
StatePublished - Dec 1 2016

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Keywords

  • CTCF
  • MNase
  • chemical biology
  • chromatin
  • embryonic stem cells
  • epigenetics
  • nucleosomes
  • pioneer transcription factors
  • pluripotency
  • splicing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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