Studies of nucleosome positioning in a variety of mutant backgrounds (see, e.g., van Bakel et al. 2013), along with insights gained from biochemical reconstitutions using histone proteins and purified DNA (Korber and Horz 2004; Sekinger et al. 2005; Kaplan et al. 2009; Zhang et al. 2011), provide insights into multiple forces that direct nucleosome positioning in vivo. First, the affinity of a given sequence for the histone octamer differs between DNA sequences based on their flexibility, with intrinsically stiff polyA/T tracts being disfavored for nucleosome incorporation and thereby “programming” nucleosome depletion. Second, nucleosome positions can be influenced by steric inhibition, either with adjacent nucleosomes or other DNA-binding proteins such as transcription factors. This can lead to local positioning cues having impacts on positions of nucleosomes some distance away, as, for example, proposed in the “statistical positioning” model for nucleosome positioning (Kornberg and Stryer 1988). Third, a broad class of regulatory factors, the ATP-dependent nucleosome remodelers, plays a key role in assembling, displacing, and evicting nucleosomes (Clapier and Cairns 2009). Finally, additional structural elements such as Heterochromatin Protein 1 (HP1) and
