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Peer-reviewedCC BYNature Communications

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

  • Jan Philipp Kreysing1,2
  • Sergio Cruz-León3
  • Johannes Betz3
  • Carlotta Penzo4
  • Tomáš Majtner1
  • Markus Schreiber1,2
  • Beata Turoňová5
  • Marina Lušić6
  • Gerhard Hummer7,8
  • Martin Beck9,10
10 affiliations
  1. 1Department of Molecular Sociology, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany
  2. 2IMPRS on Cellular Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany
  3. 3Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany
  4. 4Department of Infectious Diseases, Integrative Virology, Heidelberg University, Heidelberg, Germany
  5. 5Department of Molecular Sociology, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany. [email protected]
  6. 6Department of Infectious Diseases, Integrative Virology, Heidelberg University, Heidelberg, Germany. [email protected]
  7. 7Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany. [email protected]
  8. 8Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany. [email protected]
  9. 9Department of Molecular Sociology, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, Frankfurt am Main, Germany. [email protected]
  10. 10Institute of Biochemistry, Goethe University Frankfurt, Frankfurt am Main, Germany. [email protected]
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{kreysing2026molecular,
  title = {{Molecular architecture of heterochromatin at the nuclear periphery of primary human cells}},
  author = {Jan Philipp Kreysing and Sergio Cruz-León and Johannes Betz and Carlotta Penzo and Tomáš Majtner and Markus Schreiber and Beata Turoňová and Marina Lušić and Gerhard Hummer and Martin Beck},
  journal = {Nature Communications},
  year = {2026},
  month = jul,
  doi = {10.1038/s41467-026-75087-5},
  url = {https://doi.org/10.1038/s41467-026-75087-5},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Molecular architecture of heterochromatin at the nuclear periphery of primary human cells
AU  - Jan Philipp Kreysing
AU  - Sergio Cruz-León
AU  - Johannes Betz
AU  - Carlotta Penzo
AU  - Tomáš Majtner
AU  - Markus Schreiber
AU  - Beata Turoňová
AU  - Marina Lušić
AU  - Gerhard Hummer
AU  - Martin Beck
PY  - 2026
DA  - 2026/07/03
JO  - Nature Communications
DO  - 10.1038/s41467-026-75087-5
UR  - https://doi.org/10.1038/s41467-026-75087-5
AB  - 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.
SN  - 2041-1723
ER  -