ArticleCommunications biology2026
Cryo-EM structures of CENP-A nucleosomes isolated from human cells.
Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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