21ME

Cryo-EM structure of heterotypic CENP-A/H3 nucleosome isolated from human cells

Summary for 21ME

• Entry DOI: 10.2210/pdb21me/pdb
• Related: 21MD
• EMDB information: 67819
• Descriptor: Histone H3-like centromeric protein A, Histone H4, Histone H2A type 1-B/E, ... (6 entities in total)
• Functional Keywords: nuclear protein, chromatin, mitosis, centromere
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 10
• Total formula weight: 156560.44

Authors

Tanida, E.,Hatazawa, S.,Oishi, T.,Kobayashi, Y.,Ogasawara, M.,Jaskiewicz, M.A.,Takizawa, Y.,Kurumizaka, H. (deposition date: 2025-12-18, release date: 2026-10-14)

Primary citation

Tanida, E.,Hatazawa, S.,Oishi, T.,Kobayashi, Y.,Ogasawara, M.,Jaskiewicz, M.A.,Harada, A.,Fujii, T.,Ohkawa, Y.,Takizawa, Y.,Kurumizaka, H.
Cryo-EM structures of CENP-A nucleosomes isolated from human cells.
Commun Biol, 9:-, 2026

PubMed Abstract: 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.

PubMed: 42811066
DOI: 10.1038/s42003-026-10946-x

Experimental method

ELECTRON MICROSCOPY (3.58 Å)