Low-throughput experiments in Drosophila using DNase I and MNase treatment, provided the first demonstration that active chromatin coincides with nuclease hypersensitivity, that is chromatin accessibility [27–30]. Currently, all chromatin accessibility assays separate the genome by enzymatic or chemical means and isolate either the accessible or protected locations. Isolated DNA is then quantified using a next-generation sequencing (NGS) platform. In this review, we focus on the latest methods for identifying chromatin accessibility genome-wide, and discuss the considerations for experimental design and data analysis. We conclude with current limitations that need to be overcome for this field to move forward.
