The first class of nucleosome-resolution assays tends to strongly enrich the relatively long linkers, known as nucleosome-depleted regions (NDRs), that are typically found at genomic regulatory elements such as promoters and enhancers. Nucleosome-depleted regions can be identified by elevated accessibility to enzymes such as the nuclease DNase I (Gross and Garrard 1988), transposases such as Tn5 (Buenrostro et al. 2013), or DNA methylases (Kelly et al. 2012). Alternatively, given the difference in protein occupancy between NDRs and bulk chromatin, physical fractionation (e.g., FAIRE) (Nagy et al. 2003) can be used to purify NDRs, as protein-enriched DNA partitions to phenol, leaving relatively protein-depleted DNA to partition to the aqueous phase.
