8y3c
Cryo-EM structure of the overlapping di-nucleosome (closed form)Cryo-EM structure of the overlapping di-nucleosome (closed form)
Structural highlights
FunctionPublication Abstract from PubMedNucleosome remodelers modify the local structure of chromatin to release the region from nucleosome-mediated transcriptional suppression. Overlapping dinucleosomes (OLDNs) are nucleoprotein complexes formed around transcription start sites as a result of remodeling, and they consist of two nucleosome moieties: a histone octamer wrapped by DNA (octasome) and a histone hexamer wrapped by DNA (hexasome). While OLDN formation alters chromatin accessibility to proteins, the structural mechanism behind this process is poorly understood. Thus, this study investigated the characteristics of structural fluctuations in OLDNs. First, multiple structures of the OLDN were visualized through cryoelectron microscopy (cryoEM), providing an overview of the tilting motion of the hexasome relative to the octasome at the near-atomistic resolution. Second, small-angle X-ray scattering (SAXS) revealed the presence of OLDN conformations with a larger radius of gyration than cryoEM structures. A more complete description of OLDN fluctuation was proposed by SAXS-based ensemble modeling, which included possible transient structures. The ensemble model supported the tilting motion of the OLDN outlined by the cryoEM models, further suggesting the presence of more diverse conformations. The amplitude of the relative tilting motion of the hexasome was larger, and the nanoscale fluctuation in distance between the octasome and hexasome was also proposed. The cryoEM models were found to be mapped in the energetically stable region of the conformational distribution of the ensemble. Exhaustive complex modeling using all conformations that appeared in the structural ensemble suggested that conformational and motional asymmetries of the OLDN result in asymmetries in the accessibility of OLDN-binding proteins. Asymmetric fluctuation of overlapping dinucleosome studied by cryoelectron microscopy and small-angle X-ray scattering.,Shimizu M, Tanaka H, Nishimura M, Sato N, Nozawa K, Ehara H, Sekine SI, Morishima K, Inoue R, Takizawa Y, Kurumizaka H, Sugiyama M PNAS Nexus. 2024 Oct 27;3(11):pgae484. doi: 10.1093/pnasnexus/pgae484. , eCollection 2024 Nov. PMID:39539301[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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