Nucleosome wrapping state encodes principles of 3D genome organization

Nucleosome is the basic structural unit of the genome. During processes like DNA replication and gene transcription, the conformation of nucleosomes undergoes dynamic changes, including DNA unwrapping and rewrapping, as well as histone disassembly and assembly. However, the wrapping characteristics of nucleosomes across the entire genome, including region-specificity and their correlation with higher-order chromatin organization, remain to be studied. In this study, we investigated the wrapping length of DNA on nucleosomes across the whole genome using wrapping-seq. We discovered that the chromatin of mouse ES cells forms Nucleosome Wrapping Domains (NRDs), which is conserved in yeast and fly. We found that the degree of nucleosome wrapping decreases after DNA replication and is promoted by transcription. Furthermore, we observed that nucleosome wrapping states delineate 3D genome organization and DNA replication timing. In conclusion, we have revealed a novel principle of higher-order chromatin organization.