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Nature, May 07 2025, | https://doi.org/10.1038/s41586-025-08971-7
Native nucleosomes intrinsically encode genome organization principles
Sangwoo Park 1, Raquel Merino-Urteaga 2,3,12, Violetta Karwacki-Neisius 2,4,12, Gustavo Ezequiel Carrizo 5,12, Advait Athreya 6,12, Alberto Marin-Gonzalez 2,4, Nils A. Benning 2,3, Jonghan Park 7, Michelle M. Mitchener 8, Natarajan V. Bhanu 9, Benjamin A. Garcia 9, Bin Zhang 10, Tom W. Muir 8, Erika L. Pearce 5,11 & Taekjip Ha 1,2,4,*
1Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA, USA.
3Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
4Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
5Department of Oncology, The Bloomberg–Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
6Computational and Systems Biology Program, MIT, Cambridge, MA, USA.
7College of Medicine, Yonsei University, Seoul, Republic of Korea.
8Department of Chemistry, Princeton University, Princeton, NJ, USA.
9Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine St. Louis, St. Louis, MO, USA.
10Department of Chemistry, MIT, Cambridge, MA, USA.
11Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
12These authors contributed equally: Raquel Merino Urteaga, Violetta Karwacki-Neisius, Gustavo Ezequiel Carrizo, Advait Athreya.
2Howard Hughes Medical Institute and Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA, USA.
3Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
4Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
5Department of Oncology, The Bloomberg–Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
6Computational and Systems Biology Program, MIT, Cambridge, MA, USA.
7College of Medicine, Yonsei University, Seoul, Republic of Korea.
8Department of Chemistry, Princeton University, Princeton, NJ, USA.
9Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine St. Louis, St. Louis, MO, USA.
10Department of Chemistry, MIT, Cambridge, MA, USA.
11Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
12These authors contributed equally: Raquel Merino Urteaga, Violetta Karwacki-Neisius, Gustavo Ezequiel Carrizo, Advait Athreya.
*Corresponding authors: correspondence to Taekjip Ha
Abstract
The eukaryotic genome is packed into nucleosomes of 147 base pairs around a histone core and is organized into euchromatin and heterochromatin, corresponding to the A and B compartments, respectively. Here we investigated whether individual nucleosomes contain sufficient information for 3D genomic organization into compartments, for example, in their biophysical properties. We purified native mononucleosomes to high monodispersity and used physiological concentrations of polyamines to determine their condensability. The chromosomal regions known to partition into A compartments have low condensability and those for B compartments have high condensability. Chromatin polymer simulations using condensability as the only input, without any trans factors, reproduced the A/B compartments. Condensability is also strongly anticorrelated with gene expression, particularly near the promoters and in a cell type-dependent manner. Therefore, mononucleosomes have biophysical properties associated with genes being on or off. Comparisons with genetic and epigenetic features indicate that nucleosome condensability is an emergent property, providing a natural axis on which to project the high-dimensional cellular chromatin state. Analysis using various condensing agents or histone modifications and mutations indicates that the genome organization principle encoded into nucleosomes is mostly electrostatic in nature. Polyamine depletion in mouse T cells, resulting from either knocking out or inhibiting ornithine decarboxylase, results in hyperpolarized condensability, indicating that when cells cannot rely on polyamines to translate the biophysical properties of nucleosomes to 3D genome organization, they accentuate condensability contrast, which may explain the dysfunction observed with polyamine deficiency.
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- Research article
- 2025년 05월 (BRIC 등록일 2025-05-09)
- 국내+국외 연구진
- 생명과학 > 구조생물 및 생물물리학
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