Genome-wide mapping and cryo-EM structural analyses of the overlapping tri-nucleosome composed of hexasome-hexasome-octasome moieties

Author:

Nishimura Masahiro,Fujii Takeru,Tanaka Hiroki,Maehara KazumitsuORCID,Morishima KenORCID,Shimizu MasahiroORCID,Kobayashi Yuki,Nozawa Kayo,Takizawa YoshimasaORCID,Sugiyama MasaakiORCID,Ohkawa YasuyukiORCID,Kurumizaka HitoshiORCID

Abstract

AbstractThe nucleosome is a fundamental unit of chromatin in which about 150 base pairs of DNA are wrapped around a histone octamer. The overlapping di-nucleosome has been proposed as a product of chromatin remodeling around the transcription start site, and previously found as a chromatin unit, in which about 250 base pairs of DNA continuously bind to the histone core composed of a hexamer and an octamer. In the present study, our genome-wide analysis of human cells suggests another higher nucleosome stacking structure, the overlapping tri-nucleosome, which wraps about 300-350 base-pairs of DNA in the region downstream of certain transcription start sites of actively transcribed genes. We determine the cryo-electron microscopy (cryo-EM) structure of the overlapping tri-nucleosome, in which three subnucleosome moieties, hexasome, hexasome, and octasome, are associated by short connecting DNA segments. Small angle X-ray scattering and coarse-grained molecular dynamics simulation analyses reveal that the cryo-EM structure of the overlapping tri-nucleosome may reflect its structure in solution. Our findings suggest that nucleosome stacking structures composed of hexasome and octasome moieties may be formed by nucleosome remodeling factors around transcription start sites for gene regulation.

Funder

MEXT | Japan Society for the Promotion of Science

Japan Agency for Medical Research and Development

MEXT | Japan Science and Technology Agency

Publisher

Springer Science and Business Media LLC

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