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 that interfere with MNase digestion, many other DNA-binding proteins provide some level of protection from nuclease digestion to the underlying sequence. In MNase-footprinting (Henikoff et al. 2011; Kent et al. 2011), the chromatin is digested, usually relatively lightly, followed by paired-end sequencing of fragments in a large size range (typically 40–400 bp). The resulting maps afford not only positions of nucleosomes and even relative nuclease access to the two edges of the nucleosome but also provide a broad survey of additional DNA-binding factors, most notably tightly bound transcription factors (TFs) that, in yeast, are known as “general regulatory factors.” Understanding the features that define strongly footprinting proteins remains an active area of analysis.
