Methods such as MNase-seq (Zaret, 2005), ChIP-seq (Landt et al., 2012), and DNase-seq (Song and Crawford, 2010) in particular have proven to be information-rich, genome-wide analysis methods for understanding this epigenetic structure, providing information on transcription factor binding, the positions of modified and canonical nucleosomes, and chromatin accessibility at regulatory elements such as promoters, enhancers, and insulators (Thurman et al., 2012; Valouev et al., 2011; Consortium, 2012). However, current methods for assaying chromatin structure and composition often require tens to hundreds of millions of cells as input material, averaging out heterogeneity in cellular populations. In many cases, rare and important cellular sub-types cannot be acquired in amounts sufficient for genome-wide chromatin analyses. The assay of transposase accessible chromatin (Buenrostro et al., 2013) (ATAC-seq) uses hyperactive Tn5 transposase (Goryshin and Reznikoff, 1998; Adey et al., 2010) to simultaneously cut and ligate adapters for high-throughput sequencing at regions of increased accessibility. Genome-wide mapping of insertion ends by high-throughput sequencing allows for multidimensional assays of the regulatory landscape of chromatin with a relatively simple protocol that can be carried out in hours for a standard sample size of 50,000 cells.
