Nucleosomal DNA has topological memory

Abstract

SUMMARYOne fundamental yet elusive aspect of the chromosome architecture is the constrained topolome, which refers to how chromatin elements restrain DNA topology. Nucleosomes stabilise negative DNA supercoils, with most nucleosomes typically restraining a DNA linking number difference (ΔLk) of about -1.26. However, whether this capacity is uniform across the genome is unknown. Here, we calculated the ΔLk restrained by over 4000 nucleosomes in yeast cells. To achieve this, we placed each nucleosome in a circular minichromosome and performed Topo-seq, a novel high-throughput procedure to inspect the topology of circular DNA libraries in a single gel electrophoresis. We found that nucleosomes inherently restrain distinct ΔLk values depending on their genomic origin. Nucleosome DNA topologies differ significantly at gene bodies (ΔLk=-1.29), intergenic regions (ΔLk=-1.23), rDNA genes (ΔLk=-1.24) and telomeric regions (ΔLk=-1.07). Nucleosomes nearby the transcription start and termination sites also exhibit singular DNA topologies. These findings demonstrate that nucleosome DNA topology is imprinted by its native chromatin context and persists even when the nucleosome is relocated. This imprinting contributes to nucleosome functional roles and chromatin folding architectures.