Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions (original) (raw)

  1. Jason D. Buenrostro1,
  2. Sarah K. Denny2,
  3. Katja Schwartz1,
  4. Gavin Sherlock1 and
  5. William J. Greenleaf1,3
  6. 1Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA;
  7. 2Biophysics Program, Stanford University School of Medicine, Stanford, California 94305, USA;
  8. 3Department of Applied Physics, Stanford University, Stanford, California 94305, USA
  9. 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

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/.