Rotational settings quantize nucleosome movement by chromatin regulators

Abstract

Proper nucleosome positioning is essential for gene regulation and genomic integrity. Regulated nucleosome assembly and positioning results from a need to protect DNA sequences genome-wide, constrained by the known intrinsic sequence preferences of histones. Current models posit that chromatin regulators override the intrinsic preferences to establish the nucleosome landscapes observed in vivo, implying minimal roles for DNA sequence in guiding nucleosomal structure in cells. In contrast, we demonstrate that DNA sequence intrinsically guides the structure and remodeling of nucleosomes from yeast to mammals. We demonstrate that nucleosomes with weak translational settings in vitro, in yeast, and in mammalian cells demonstrate a clear preference for inward-facing A/T dinucleotides and outward facing G/C dinucleotides, at 10 bp spacings consistent with established preferences for rotationally positioned nucleosomes. Foreign DNA sequences heterologously inserted into the yeast genome obey similar rules, indicating that DNA sequence itself is causal. Finally, remodelers and transcription elongation change the preference among the alternative translational positions 10 bp apart, retaining the rotational setting. From these results, we propose that DNA sequence creates an energy landscape with preferred rotational settings every [~]10 bp, and that chromatin regulators, rather than overriding these preferences, navigate within them. This "detent" mechanism provides a unifying framework for understanding how diverse cellular processes achieve precise nucleosome positioning while maintaining the same DNA face exposed to regulatory factors.