Eukaryotic genomes are functionally organized into chromatin, a compact packaging of nucleoproteins with the basic repeating unit known as the nucleosome. A major focus for the chromatin field has been understanding what rules govern nucleosome positioning throughout the genome, and here we review recent findings using a novel, sequence‐targeted remodeling enzyme. Nucleosomes are often packed into evenly spaced arrays that are reproducibly positioned, but how such organization is established and maintained through dramatic events such as DNA replication is poorly understood. (...) We hypothesize that a major fraction of positioned nucleosomes arises from sequence‐specific targeting of chromatin remodelers to generate “founding” nucleosomes, providing reproducible, predictable, and condition‐specific nucleation sites against which neighboring nucleosomes are packed into evenly spaced arrays. (shrink)