| dc.description.abstract | Nucleosomes, the basic units of chromatin in eukaryotes, play a critical role in DNA processing such as transcription, replication, and repair. The canonical nucleosome core particle consists of 145 to 147 DNA base pairs wrapped around a histone octamer composed of one (H3-H4)₂ tetramer and two H2A-H2B dimers. This arrangement results in two stacked disks. Although the importance of non-canonical structures with alternative histone conformations in controlling genome organization and regulation has been recognized, our knowledge of them remains limited. In a recent development, unconventional nucleoprotein particles composed of only two types of histones (H3-H4 or CENP-A-H4) have been identified through cryo-electron microscopy. Here, all-atom molecular dynamics simulations are performed on single nucleosome units to elucidate the specific dynamic properties of the octamers forming a di-tetrameric core. The analysis shows that these structures exhibit significant DNA unwrapping compared to the canonical nucleosome. In particular, the histone H3 variant CENP-A, which marks the location of the centromere, shows the most excessive unwrapping of DNA ends from the core, resulting in an almost orthogonal arrangement of the DNA entry/exit sites. The pronounced flexibility for the last ∼ 20 base pairs observed in the simulations is related to the increased interdisk spacing of the DNA superhelical gyres, which is about one and a half times larger than in the corresponding nucleosome core particle with histones H3 or CENP-A. The results consistently indicate that the di-tetrameric stoichiometry of H3-H4 or CENP-A-H4 leads to increased dynamics and to an opening of the core particle, potentially allowing greater access to DNA binding factors. | eng |