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<p>In eukaryotes, meters of DNA are packaged into micrometer scale nuclei. Nucleosomes, as the major organizational unit, have been extensively studied in vitro, yet the elaborate 3D structure of chromatin inside cells and its distinct oligo-nucleosome arrangements remain poorly resolved. Here, we combine cryo-electron tomography with template matching, subtomogram averaging and molecular simulations to visualize nucleosomes and chromatin structure inside human cells. We confidently assign individual nucleosomes and report their in-situ structure at secondary structure resolution. By predicting the paths of linker DNA, we identify oligo-nucleosome arrangements and uncover higher-order chromatin structures in situ, including a 37-nm wide, elongated but non-fibrous arrangement. In situ structural biology thus reveals the molecular chromatin organization inside cells and sets the stage for 3D genomics.</p>

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Molecular architecture of heterochromatin at the nuclear periphery of primary human cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月3日

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  • Jan Philipp Kreysing,
  • Sergio Cruz-León,
  • Johannes Betz,
  • Carlotta Penzo,
  • Tomáš Majtner,
  • Markus Schreiber,
  • Beata Turoňová,
  • Marina Lusic,
  • Gerhard Hummer,
  • Martin Beck

摘要

In eukaryotes, meters of DNA are packaged into micrometer scale nuclei. Nucleosomes, as the major organizational unit, have been extensively studied in vitro, yet the elaborate 3D structure of chromatin inside cells and its distinct oligo-nucleosome arrangements remain poorly resolved. Here, we combine cryo-electron tomography with template matching, subtomogram averaging and molecular simulations to visualize nucleosomes and chromatin structure inside human cells. We confidently assign individual nucleosomes and report their in-situ structure at secondary structure resolution. By predicting the paths of linker DNA, we identify oligo-nucleosome arrangements and uncover higher-order chromatin structures in situ, including a 37-nm wide, elongated but non-fibrous arrangement. In situ structural biology thus reveals the molecular chromatin organization inside cells and sets the stage for 3D genomics.