Rotational settings quantize nucleosome movement by chromatin regulators

Proper nucleosome positioning is essential for gene regulation and genomic integrity. The need for nucleosomes to be assembled throughout the genome has to be balanced with known intrinsic sequence preferences of nucleosomes. Current models posit that chromatin regulators override the intrinsic preferences to establish the nucleosome landscapes observed in vivo. Here, in contrast, we find that chromatin regulators take advantage of both the preference of the nucleosomes for A/T dinucleotides to face inward and G/C outward every 10 bp relative to the histone surface and the existing dinucleotide frequencies of the genome to move nucleosomes in discrete 10 bp steps. We find that the rotational settings of nucleosomes are identical in vivo and in vitro in yeast. Remodelers and transcription elongation change the preference among the alternative translational positions 10 bp apart that a given rotational setting allows. Our results support a model where strong rotational settings introduce a 10 bp ratchet for nucleosome mobilization, leading to quantized shifts in nucleosome positions in yeast and mouse cells. Overall design: MNase-seq of wild-type mouse embryonic stem cells with multiple time-points