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TitleCryo-EM structures of CENP-A nucleosomes isolated from human cells.
Journal, issue, pagesCommun Biol, Vol. 9, Issue 1, Year 2026
Publish dateSep 29, 2026
AuthorsEisho Tanida / Suguru Hatazawa / Takumi Oishi / Yuki Kobayashi / Mitsuo Ogasawara / Marta A Jaskiewicz / Akihito Harada / Takeru Fujii / Yasuyuki Ohkawa / Yoshimasa Takizawa / Hitoshi Kurumizaka /
PubMed AbstractCentromeres ensure accurate chromosome segregation, and their identity is specified epigenetically by the histone H3 variant CENP-A. Although the structures of reconstituted CENP-A nucleosomes have ...Centromeres ensure accurate chromosome segregation, and their identity is specified epigenetically by the histone H3 variant CENP-A. Although the structures of reconstituted CENP-A nucleosomes have provided important insights, how this epigenetic mark is structurally organized within native chromatin remains incompletely understood. Here, we combine cryogenic electron microscopy with chromatin immunoprecipitation (ChIP-CryoEM) to determine the structures of human CENP-A nucleosomes isolated directly from cells without crosslinking or stabilizing agents. We resolved two distinct cellular CENP-A nucleosome structures: a homotypic CENP-A nucleosome and a heterotypic CENP-A/H3 nucleosome, which have been proposed to represent centromeric and ectopic nucleosomes, respectively. Both cellular CENP-A nucleosomes assemble as histone octamers and wrap DNA in a left-handed superhelix, supporting an octameric model proposed for native CENP-A chromatin. In addition, the hallmark CENP-A-specific structural features previously characterized in vitro, including the shortened CENP-A N-terminal α-helix and the distinctive RG loop, are preserved in cellular CENP-A nucleosomes. These findings define the structural organization of CENP-A nucleosomes in cellular chromatin.
External linksCommun Biol / PubMed:42811066 / PubMed Central
MethodsEM (single particle)
Resolution3.12 - 3.58 Å
Structure data

67818

21md

EMDB-67818, PDB-21md:
Cryo-EM structure of homotypic CENP-A nucleosome isolated from human cells
Method: EM (single particle) / Resolution: 3.12 Å

67819

21me

EMDB-67819, PDB-21me:
Cryo-EM structure of heterotypic CENP-A/H3 nucleosome isolated from human cells
Method: EM (single particle) / Resolution: 3.58 Å

Source
  • homo sapiens (human)
KeywordsNUCLEAR PROTEIN / chromatin / mitosis / centromere

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