Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions
- Alicia N. Schep1,
- Jason D. Buenrostro1,
- Sarah K. Denny2,
- Katja Schwartz1,
- Gavin Sherlock1 and
- William J. Greenleaf1,3
- 1Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;
- 2Biophysics Program, Stanford University School of Medicine, Stanford, California 94305, USA;
- 3Department of Applied Physics, Stanford University, Stanford, California 94305, USA
- Corresponding author: wjg{at}stanford.edu
Abstract
Transcription factors canonically bind nucleosome-free DNA, making the positioning of nucleosomes within regulatory regions crucial to the regulation of gene expression. Using the assay of transposase accessible chromatin (ATAC-seq), we observe a highly structured pattern of DNA fragment lengths and positions around nucleosomes in Saccharomyces cerevisiae, and use this distinctive two-dimensional nucleosomal “fingerprint” as the basis for a new nucleosome-positioning algorithm called NucleoATAC. We show that NucleoATAC can identify the rotational and translational positions of nucleosomes with up to base-pair resolution and provide quantitative measures of nucleosome occupancy in S. cerevisiae, Schizosaccharomyces pombe, and human cells. We demonstrate the application of NucleoATAC to a number of outstanding problems in chromatin biology, including analysis of sequence features underlying nucleosome positioning, promoter chromatin architecture across species, identification of transient changes in nucleosome occupancy and positioning during a dynamic cellular response, and integrated analysis of nucleosome occupancy and transcription factor binding.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.192294.115.
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Freely available online through the Genome Research Open Access option.
- Received March 20, 2015.
- Accepted August 21, 2015.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
