Determinants of nucleosome organization in primary human cells. Nature 474

Nucleosomes are the basic packaging units of chromatin, modulating accessibility of regulatory proteins to DNA and thus influencing eukaryotic gene regulation. Elaborate chromatin remodeling mechanisms have evolved that govern nucleosome organization at promoters, regulatory elements, and other functional regions in the genome1. Analyses of chromatin landscape have uncovered a variety of mechanisms, including DNA sequence preferences, that can influence nucleosome positions2–4. To identify major determinants of nucleosome organization in the human genome, we utilized deep sequencing to map nucleosome positions in three primary human cell types and in vitro. A majority of the genome exhibited substantial flexibility of nucleosome positions while a small fraction showed reproducibly positioned nucleosomes. Certain sites that position in vitro can anchor the formation of nucleosomal arrays that have cell type-specific spacing in vivo. Our results unveil an interplay of sequence-based nucleosome preferences and non-nucleosomal factors in determining nucleosome organization within mammalian cells. Previous studies in model organisms3–7 as well as initial analyses in human cells8 have identified fundamental aspects of nucleosome organization. We here focus on the dynamic relationships between sequence-based nucleosome preferences and chromatin regulatory function in primary human cells. We mapped tissue-specific and DNA-encoded nucleosome organization across granulocytes and two types of T-cells (CD4+ and CD8+) isolated from the blood of a single human donor, by isolating cellular chromatin and treating it with micrococcal nuclease (MNase) followed by deep sequencing of the resulting nucleosome-protected fragments (Methods, Supplementary Fig. 1). To provide sufficient depth for bot