Histone octamer rearranges to adapt to DNA unwrapping

Nucleosomes, the basic unit of chromatin, package and regulate expression of eukaryotic genomes. Although the structure of the intact nucleosome has been studied, little is known about structures of its partially unwrapped, transient intermediates. In this study, we present 9 cryo EM structures of distinct conformations of nucleosome and subnucleosome particles. Our structures show that initial DNA breathing induces conformational changes in the histone octamer, particularly in histone H3, that propagate through the nucleosome and prevent symmetrical DNA opening. Rearrangements in the H2A–H2B dimer strengthen interaction with the unwrapping DNA and promote nucleosome stability. In agreement, cross-linked H2A–H2B that can not accommodate to the unwrapping of the DNA is not stably maintained in the nucleosome. H2A–H2B release and DNA unwrapping occur simultaneously indicating that DNA is essential in stabilizing the dimer in the nucleosome. Our structures reveal intrinsic nucleosomal plasticity that is required for nucleosome stability and might be exploited by extrinsic protein factors.