A computational approach to map nucleosome positions and alternative chromatin states with base pair resolution

Abstract
Data availability
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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

The following data sets were generated

1. Xu Zhou
2. Erin O'Shea
(2013) A template-based Bayesian method for identifying nucleosome positions at base-pair resolution
Publicly available at the NCBI Short Read Archive (accession no: SRX286351).

http://www.ncbi.nlm.nih.gov/sra/SRX286351/

The following previously published data sets were used

1. Brogaard KR
2. Xi L
3. Wang J
4. Widom J
(2012) A map of nucleosome positions in yeast at base-pair resolution
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE36063).

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36063
1. Rhee HS
2. Pugh BF
(2012) Genome-wide structure and organization of eukaryotic pre-initiation complexes
Publicly available at the NCBI Sequence Read Archive (accession no: SRA046523).

http://trace.ncbi.nlm.nih.gov/Traces/sra/?study=SRP010134
1. Jiang C
2. Pugh BF
(2009) reference A systematic reference map of nucleosome positions across the Saccharomyces genome
website database.

http://atlas.bx.psu.edu/project/saccharomyces.html

Article and author information

Author details

Xu Zhou

Yale School of Medicine, New Haven, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-1692-6823
Alexander W Blocker

Department of Statistics, Harvard University, Cambridge, United States

Competing interests
No competing interests declared.
Edoardo M Airoldi

Department of Statistics, Harvard University, Cambridge, United States

For correspondence
airoldi@fas.harvard.edu

Competing interests
No competing interests declared.
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.

"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.

Copyright

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.