Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions

Abstract

Transcription factors canonically bind nucleosome-free DNA, making the positioning of nucleosomes within regulatory regions crucial to the regulation of gene expression. We observe a highly structured pattern of DNA fragment lengths and positions generated by the assay of transposase accessible chromatin (ATAC-seq) around nucleosomes in S. 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, S. pombe, and human cells. We demonstrate 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.