The assays in the second class target the locations of individual nucleosomes. The most common tool for such analysis is micrococcal nuclease (MNase) digestion. This nuclease has preference for linker DNA over nucleosomal DNA (Noll and Kornberg 1977), and size separation of the DNA fragments remaining after MNase digestion results in a regular “ladder” with repeating unit size. Sequencing the resulting mononucleosome-sized fragments (MNase-seq) then provides a catalog of nucleosome-protected regions (Hughes and Rando 2014), revealing both locations of “well-positioned” nucleosomes that are present in the same location in most of the cell population, and locations of “fuzzy” regions where the nucleosome location varies between cells. Beyond the location and occupancy of nucleosomes, more nuanced details of nucleosomal organization can be gleaned from a thorough analysis of nuclease digestion products. Most notably, in addition to the stable nucleosomes revealed in typical MNase digestion reactions, a more labile subset of “fragile” nucleosomes is obtained only after relatively light MNase digestion of chromatin (Weiner et al. 2010; Xi et al. 2011). Moreover, while nucleosomes are by far the most widespread DNA-binding factors
