A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution
- Yale School of Medicine, United States
- Harvard University, United States
- Howard Hughes Medical Institute, Harvard University, United States
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.
Data availability
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A template-based Bayesian method for identifying nucleosome positions at base-pair resolutionPublicly available at the NCBI Short Read Archive (accession no: SRX286351).
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A map of nucleosome positions in yeast at base-pair resolutionPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE36063).
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Genome-wide structure and organization of eukaryotic pre-initiation complexesPublicly available at the NCBI Sequence Read Archive (accession no: SRA046523).
Article and author information
Author details
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
- Asifa Akhtar, Max Planck Institute for Immunobiology and Epigenetics, Germany
Version history
- Received: April 15, 2016
- Accepted: September 13, 2016
- Accepted Manuscript published: September 13, 2016 (version 1)
- 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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A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution
eLife 5:e16970.
https://doi.org/10.7554/eLife.16970
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