discuss chromatin accessibility assays that directly (DNase-seq, FAIRE-seq and ATAC-seq) isolate accessible locations of a genome separate from MNase-seq, which indirectly evaluates chromatin accessibility, and present their principal mode of action, examples of application and main experimental considerations (Table 1).Table 1 Current genome-wide high-throughput chromatin accessibility assays Cell type/NumberSequencing typeTraditional approachGenomic targetExperimental considerationsKey references MNase-seq Any cell type 1 to 10 million cellsPaired-end or Single-endMNase digests unprotected DNAMaps the total nucleosome population in a qualitative and quantitative manner1. Requires many cells.[37, 46, 49]2. Laborious enzyme titrations.3. Probes total nucleosomal population, not active regulatory regions only.4. Degrades active regulatory regions, making their detection possible only indirectly.5. Requires 150 to 200 million reads for standard accessibility studies of the human genome. DNase-seq Any cell type 1 to 10 million cellsPaired-end or Single-endDNase I cuts within unprotected DNAMaps open chromatin1. Requires many cells.[61, 75, 76]2. Time-consuming and complicated sample preparations.3. Laborious enzyme titrations.4. Requires 20 to 50 million reads for standard accessibility studies of the human genome. FAIRE-seq Any cell type 100,000 to 10 million cellsPaired-end or Single-endBased on the phenol-chloroform separation of nucleosome-bound and free sonicated areas of a genome, in the interphase and aqueous phase respectivelyMaps open chromatin1. Low signal-to-noise ratio,
