1. Computational and Systems Biology
  2. Genetics and Genomics
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A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution

  1. Xu Zhou
  2. Alexander W Blocker
  3. Edoardo M Airoldi  Is a corresponding author
  4. Erin K O'Shea  Is a corresponding author
  1. Yale School of Medicine, United States
  2. Harvard University, United States
  3. Howard Hughes Medical Institute, Harvard University, United States
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Cite this article as: eLife 2016;5:e16970 doi: 10.7554/eLife.16970

Abstract

Understanding chromatin function requires knowing the precise location of nucleosomes. MNase-seq methods have been widely applied to characterize nucleosome organization in vivo, but generally lack the accuracy to determine the precise nucleosome positions. Here we develop a computational approach leveraging digestion variability to determine nucleosome positions at base-pair resolution from MNase-seq data. We generate a variability template as a simple error model for how MNase digestion affects mapping of individual nucleosomes. Applied to both yeast and human cells, this analysis reveals that alternatively positioned nucleosomes are prevalent and create significant heterogeneity in a cell population. We show that the periodic occurrences of dinucleotide sequences relative to nucleosome dyads can be directly determined from genome-wide nucleosome positions from MNase-seq. Alternatively positioned nucleosomes near transcription start sites likely represent different states of promoter nucleosomes during transcription initiation. Our method can be applied to map nucleosome positions in diverse organisms at base-pair resolution.

Article and author information

Author details

  1. Xu Zhou

    Yale School of Medicine, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1692-6823
  2. Alexander W Blocker

    Department of Statistics, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  3. Edoardo M Airoldi

    Department of Statistics, Harvard University, Cambridge, United States
    For correspondence
    airoldi@fas.harvard.edu
    Competing interests
    No competing interests declared.
  4. Erin K O'Shea

    Faculty of Arts and Sciences Center for Systems Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, United States
    For correspondence
    osheae@hhmi.org
    Competing interests
    Erin K O'Shea, President at the Howard Hughes Medical Institute, one of the three founding funders of eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2649-1018

Funding

Howard Hughes Medical Institute

  • Xu Zhou
  • Erin K O'Shea

National Institute of General Medical Sciences (GM-096193)

  • Alexander W Blocker
  • Edoardo M Airoldi

Alfred P. Sloan Foundation

  • Alexander W Blocker
  • Edoardo M Airoldi

Jane Coffin Childs Memorial Fund for Medical Research

  • Xu Zhou

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Asifa Akhtar, Max Planck Institute for Immunobiology and Epigenetics, Germany

Publication history

  1. Received: April 15, 2016
  2. Accepted: September 13, 2016
  3. Accepted Manuscript published: September 13, 2016 (version 1)
  4. Version of Record published: September 30, 2016 (version 2)

Copyright

© 2016, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

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