Bintu, B. et al.
Beliveau, B. J. et al.
Schultz, E. R., Kyhl, S., Willett, R. & de Pablo, J. J. Chromatin structures from integrated AI and polymer physics model.
Paggi, J. Simulation trajectories for ‘Euchromatin forms condensed domains with short active regions on the surface’ [Dataset].
Code archive for ‘Euchromatin forms condensed domains with short active regions on the surface’ [Computer software].
Miron, E. et al. Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin. Sci. Adv. 6, eaba8811 (2020).
Maeshima, K., Iida, S., Shimazoe, M. A., Tamura, S. & Ide, S. Is euchromatin really open in the cell? Trends Cell Biol. 34, 7–17 (2024).
Nozaki, T. et al. Condensed but liquid-like domain organization of active chromatin regions in living human cells. Sci. Adv. 9, eadf1488 (2023).
Gelléri, M. et al. True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin. Cell Rep. 42, 112567 (2023).
Paggi, J. M. & Zhang, B. Toward decoding the mechanisms that shape sub-megabase-scale genome organization. Curr. Opin. Struct. Biol. 92, 103062 (2025).
Ricci, M. A., Manzo, C., García-Parajo, M. F., Lakadamyali, M. & Cosma, M. P. Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo. Cell 160, 1145–1158 (2015).
Ou, H. D. et al. ChromEMT: visualizing 3D chromatin structure and compaction in interphase and mitotic cells. Science 357, eaag0025 (2017).
Hou, Z., Nightingale, F., Zhu, Y., MacGregor-Chatwin, C. & Zhang, P. Structure of native chromatin fibres revealed by Cryo-ET in situ. Nat. Commun. 14, 6324 (2023).
Li, Y., Zhang, H., Li, X., Wu, W. & Zhu, P. Cryo-ET study from in vitro to in vivo revealed a general folding mode of chromatin with two-start helical architecture. Cell Rep. 42, 113134 (2023).
Kreysing, J. P. et al. Molecular architecture of heterochromatin at the nuclear periphery of primary human cells. Nat. Commun. 17, 5844 (2026).
Chen, J. K. Nanoscale analysis of human G1 and metaphase chromatin in situ. EMBO J. 44, 12 https://doi.org/10.1038/s44318-025-00407-2 (2025).
Li, W. S. et al. Mature chromatin packing domains persist after RAD21 depletion in 3D. Sci. Adv. 11, eadp0855 (2025).
Bintu, B. et al. Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells. Science 362, eaau1783 (2018).
Szabo, Q. et al. Regulation of single-cell genome organization into TADs and chromatin nanodomains. Nat. Genet. 52, 1151–1157 (2020).
Lakadamyali, M. & Cosma, M. P. Visualizing the genome in high resolution challenges our textbook understanding. Nat. Methods 17, 371–379 (2020).
Beliveau, B. J. et al. Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes. Nat. Commun. 6, 7147 (2015).
Takei, Y. et al. Spatial multi-omics reveals cell-type-specific nuclear compartments. Nature 641, 1037–1047 (2025).
Dekker, J., Rippe, K., Dekker, M. & Kleckner, N. Capturing chromosome conformation. Science 295, 1306–1311 (2002).
Lieberman-Aiden, E. et al. Comprehensive mapping of long range interactions reveals folding principles of the human genome. Science 326, 289–293 (2009).
Tan, L., Xing, D., Chang, C.-H., Li, H. & Xie, X. S. Three-dimensional genome structures of single diploid human cells. Science 361, 924–928 (2018).
Beagrie, R. A. et al. Complex multi-enhancer contacts captured by genome architecture mapping. Nature 543, 519–524 (2017).
Quinodoz, S. A. et al. Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus. Cell 174, 744–757.e24 (2018).
Hsieh, T.-H. S. et al. Mapping nucleosome resolution chromosome folding in yeast by Micro-C. Cell 162, 108–119 (2015).
Ohno, M. et al. Sub-nucleosomal genome structure reveals distinct nucleosome folding motifs. Cell 176, 520–534.e25 (2019).
Krietenstein, N. et al. Ultrastructural details of mammalian chromosome architecture. Mol. Cell 78, 554–565.e7 (2020).
Hsieh, T.-H. S. et al. Resolving the 3D landscape of transcription-linked mammalian chromatin folding. Mol. Cell 78, 539–553.e8 (2020).
Shi, G. & Thirumalai, D. From Hi-C contact map to three-dimensional organization of interphase human chromosomes. Phys. Rev. X 11, 011051 (2021).
Kadam, S. et al. Predicting scale-dependent chromatin polymer properties from systematic coarse-graining. Nat. Commun. 14, 4108 (2023).
Boninsegna, L. et al. Integrative genome modeling platform reveals essentiality of rare contact events in 3D genome organizations. Nat. Methods 19, 938–949 (2022).
Nuebler, J., Fudenberg, G., Imakaev, M., Abdennur, N. & Mirny, L. A. Chromatin organization by an interplay of loop extrusion and compartmental segregation. Proc. Natl Acad. Sci. USA 115, E6697–E6706 (2018).
Di Pierro, M., Zhang, B., Aiden, E. L., Wolynes, P. G. & Onuchic, J. N. Transferable model for chromosome architecture. Proc. Natl Acad. Sci. USA 113, 12168–12173 (2016).
Di Pierro, M., Cheng, R. R., Lieberman Aiden, E., Wolynes, P. G. & Onuchic, J. N. De novo prediction of human chromosome structures: epigenetic marking patterns encode genome architecture. Proc. Natl Acad. Sci. USA 114, 12126–12131 (2017).
Chiang, M. et al. Genome-wide chromosome architecture prediction reveals biophysical principles underlying gene structure. Cell Genom. 4, 100698 (2024).
Salari, H., Fourel, G. & Jost, D. Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization. Nat. Commun. 15, 5393 (2024).
Fiorillo, L. et al. Comparison of the Hi-C, GAM and SPRITE methods using polymer models of chromatin. Nat. Methods 18, 482–490 (2021).
Neguembor, M. V. et al. MiOS, an integrated imaging and computational strategy to model gene folding with nucleosome resolution. Nat. Struct. Mol. Biol. 29, 1011–1023 (2022).
Wakim, J. G. & Spakowitz, A. J. Physical modeling of nucleosome clustering in euchromatin resulting from interactions between epigenetic reader proteins. Proc. Natl Acad. Sci. USA 121, e2317911121 (2024).
Brahmachari, S., Contessoto, V. G., Di Pierro, M. & Onuchic, J. N. Shaping the genome via lengthwise compaction, phase separation, and lamina adhesion. Nucleic Acids Res. 50, 4258–4271 (2022).
Goychuk, A., Kannan, D., Chakraborty, A. K. & Kardar, M. Polymer folding through active processes recreates features of genome organization. Proc. Natl Acad. Sci. USA 120, e2221726120 (2023).
Chu, X. & Wang, J. Deciphering the molecular mechanism of the cancer formation by chromosome structural dynamics. PLoS Comput. Biol. 17, e1009596 (2021).
Portillo-Ledesma, S., Li, Z. & Schlick, T. Genome modeling: from chromatin fibers to genes. Curr. Opin. Struct. Biol. 78, 102506 (2023).
Brandani, G. B., Gu, C., Gopi, S. & Takada, S. Multiscale Bayesian simulations reveal functional chromatin condensation of gene loci. PNAS Nexus 3, pgae226 (2024).
Schultz, E. R., Kyhl, S., Willett, R. & de Pablo, J. J. Chromatin structures from integrated AI and polymer physics model. PLoS Comput. Biol. 21, e1012912 (2025).
Zhang, B. & Wolynes, P. G. Topology, structures, and energy landscapes of human chromosomes. Proc. Natl Acad. Sci. USA 112, 6062–6067 (2015).
Lin, X., Qi, Y., Latham, A. P. & Zhang, B. Multiscale modeling of genome organization with maximum entropy optimization. J. Chem. Phys. 155, 010901 (2021).
Shin, S., Shi, G. & Thirumalai, D. From effective interactions extracted using Hi-C data to chromosome structures in conventional and inverted nuclei. PRX Life 1, 013010 (2023).
Schuette, G., Ding, X. & Zhang, B. Efficient Hi-C inversion facilitates chromatin folding mechanism discovery and structure prediction. Biophys. J. 122, 3425–3438 https://doi.org/10.1016/j.bpj.2023.07.017 (2023).
Xie, W. J. & Zhang, B. Learning the formation mechanism of domain-level chromatin states with epigenomics data. Biophys. J. 116, 2047–2056 (2019).
Goel, V. Y., Huseyin, M. K. & Hansen, A. S. Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments. Nat. Genet. 55, 1048–1056 (2023).
Hong, C. K. Y., Feng, F., Ramanathan, V., Liu, J. & Hansen, A. S. Genome structure mapping with high-resolution 3D genomics and deep learning. Preprint at bioRxiv https://doi.org/10.1101/2025.05.06.650874 (2025).
Goel, V. Y. et al. Dynamics of microcompartment formation at the mitosis-to-G1 transition. Nat. Struct. Mol. Biol. 32, 2614–2627 https://doi.org/10.1038/s41594-025-01687-2 (2025).
Imakaev, M. et al. Iterative correction of Hi-C data reveals hallmarks of chromosome organization. Nat. Methods 9, 999–1003 (2012).
Knight, P. A. & Ruiz, D. A fast algorithm for matrix balancing. IMA J. Numer. Anal. 33, 1029–1047 (2013).
Yang, J. H. & Hansen, A. S. Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation. Nat. Rev. Mol. Cell Biol. 25, 574–591 (2024).
Park, S. et al. Native nucleosomes intrinsically encode genome organization principles. Nature 643, 572–581 (2025).
Xu, J. et al. Super-resolution imaging of higher-order chromatin structures at different epigenomic states in single mammalian cells. Cell Rep. 24, 873–882 (2018).
Fukai, Y. T. et al. Gene-scale in vitro reconstitution reveals histone acetylation directly controls chromatin architecture. Sci. Adv. 11, eadx9282 (2025).
Ishihara, S. et al. Local states of chromatin compaction at transcription start sites control transcription levels. Nucleic Acids Res. 49, 8007–8023 (2021).
Schwartz, U. et al. Characterizing the nuclease accessibility of DNA in human cells to map higher order structures of chromatin. Nucleic Acids Res. 47, 1239–1254 (2019).
Falk, M. et al. Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature 570, 395–399 (2019).
Jaynes, E. T. Information theory and statistical mechanics. II. Phys. Rev. 108, 171–190 (1957).
Xingcheng, L. & Bin, Z. Explicit ion modeling predicts physicochemical interactions for chromatin organization. eLife 12, RP90073 (2023).
Tavares-Cadete, F., Norouzi, D., Dekker, B., Liu, Y. & Dekker, J. Multi-contact 3C reveals that the human genome during interphase is largely not entangled. Nat. Struct. Mol. Biol. 27, 1105–1114 (2020).
Fujimori, T. et al. Single-cell chromatin state transitions during epigenetic memory formation. Sci. Adv. 12, eaeb0060 (2026).
Hafner, A. et al. Loop stacking organizes genome folding from TADs to chromosomes. Mol. Cell 83, 1377–1392.e6 (2023).
Li, J. et al. Single-gene imaging links genome topology, promoter–enhancer communication and transcription control. Nat. Struct. Mol. Biol. 27, 1032–1040 (2020).
Huang, H. et al. CTCF mediates dosage- and sequence-context-dependent transcriptional insulation by forming local chromatin domains. Nat. Genet. 53, 1064–1074 (2021).
Roux, B. & Weare, J. On the statistical equivalence of restrained-ensemble simulations with the maximum entropy method. J. Chem. Phys. 138, 084107 (2013).
Ester, M., Kriegel, H.-P., Sander, J. & Xu, X. A density-based algorithm for discovering clusters in large spatial databases with noise. In Proc. 2nd International Conference on Knowledge Discovery and Data Mining (eds Simoudis, E. et al.) 226–231 (AAAI Press, 1996).
Li, Y. et al. Analysis of three-dimensional chromatin packing domains by chromatin scanning transmission electron microscopy (ChromSTEM). Sci Rep. 12, 12198 (2022).
Luppino, J. M. et al. Cohesin promotes stochastic domain intermingling to ensure proper regulation of boundary-proximal genes. Nat. Genet. 52, 840–848 (2020).
Conte, M. et al. Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation. Nat. Commun. 11, 3289 (2020).
Zhang, M. et al. Molecular organization of the early stages of nucleosome phase separation visualized by cryo-electron tomography. Mol. Cell 82, 3000–3014.e9 (2022).
Jentink, N., Purnell, C., Kable, B., Swulius, M. T. & Grigoryev, S. A. Cryoelectron tomography reveals the multiplex anatomy of condensed native chromatin and its unfolding by histone citrullination. Mol. Cell 83, 3236–3252.e7 (2023).
Otterstrom, J. et al. Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo. Nucleic Acids Res. 47, 8470–8484 (2019).
Castells-Garcia, A. et al. Super resolution microscopy reveals how elongating RNA polymerase II and nascent RNA interact with nucleosome clutches. Nucleic Acids Res. 50, 175–190 (2022).
Boettiger, A. N. et al. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529, 418–422 (2016).
Murphy, S. E. & Boettiger, A. N. Polycomb repression of Hox genes involves spatial feedback but not domain compaction or phase transition. Nat. Genet. 56, 493–504 (2024).
Harris, H. L. et al. Chromatin alternates between A and B compartments at kilobase scale for subgenic organization. Nat. Commun. 14, 3303 (2023).
Takei, Y. et al. Integrated spatial genomics reveals global architecture of single nuclei. Nature 590, 344–350 (2021).
Daugird, T. A. et al. Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment. Nat. Commun. 15, 4178 (2024).
Spracklin, G. et al. Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers. Nat. Struct. Mol. Biol. 30, 38–51 (2023).
Cremer, M. et al. Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters. Epigenetics Chromatin 10, 39 (2017).
Iida, S. et al. Cohesin prevents local mixing of condensed euchromatic domains in living human cells. Nat Genet. 58, 2335–2349 (2026).
Rubinstein, M. & Colby, R. H. Polymer Physics (Oxford University Press, 2003).
Oberbeckmann, E., Quililan, K., Cramer, P. & Oudelaar, A. M. In vitro reconstitution of chromatin domains shows a role for nucleosome positioning in 3D genome organization. Nat. Genet. 56, 483–492 https://doi.org/10.1038/s41588-023-01649-8 (2024).
Wiese, O., Marenduzzo, D. & Brackley, C. A. Nucleosome positions alone can be used to predict domains in yeast chromosomes. Proc. Natl Acad. Sci. USA 116, 17307–17315 (2019).
Portillo-Ledesma, S. et al. Nucleosome clutches are regulated by chromatin internal parameters. J. Mol. Biol. 433, 166701 (2021).
Li, H. et al. Mapping chromatin structure at base-pair resolution unveils a unified model of cis-regulatory element interactions. Cell 188, 7175–7193.e19 (2025).
Beckwith, K. S. et al. Nanoscale 3D DNA tracing in non-denatured cells resolves the cohesin-dependent loop architecture of the genome in situ. Nat. Commun. 16, 6673 (2025).
Chan, B. & Rubinstein, M. Theory of chromatin organization maintained by active loop extrusion. Proc. Natl Acad. Sci. USA 120, e2222078120 (2023).
Rao, S. S. P. et al. A 3D Map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014).
Oksuz, B. A. et al. Systematic evaluation of chromosome conformation capture assays. Nat. Methods 18, 1046–1055 (2021).
Kamat, K. et al. Compartmentalization with nuclear landmarks yields random, yet precise, genome organization. Biophys. J. 122, 1376–1389 (2023).
Lao, Z., Kamat, K., Jiang, Z. & Zhang, B. OpenNucleome for high resolution nuclear structural and dynamical modeling. eLife 13, RP93223 (2024).
Dombrowski, M., Engeholm, M., Dienemann, C., Dodonova, S. & Cramer, P. Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory. Nat. Struct. Mol. Biol. 29, 493–501 (2022).
Liu, S., Athreya, A., Lao, Z. & Zhang, B. From nucleosomes to compartments: physicochemical interactions underlying chromatin organization. Annu. Rev. Biophys. 53, 221–245 (2024).
Hildebrand, E. M. et al. Mitotic chromosomes are self-entangled and disentangle through a topoisomerase-II-dependent two-stage exit from mitosis. Mol. Cell 84, 1422–1441.e14 (2024).
Eastman, P. et al. OpenMM 8: molecular dynamics simulation with machine learning potentials. J. Phys. Chem. B 128, 109–116 (2024).
Zhang, Z., Liu, X., Yan, K., Tuckerman, M. E. & Liu, J. Unified efficient thermostat scheme for the canonical ensemble with holonomic or isokinetic constraints via molecular dynamics. J. Phys. Chem. A 123, 6056–6079 (2019).
Paggi, J. Simulation trajectories for ‘Euchromatin forms condensed domains with short active regions on the surface’ [Dataset]. Zenodo https://doi.org/10.5281/zenodo.16910934 (2025).
Paggi, J. Code archive for ‘Euchromatin forms condensed domains with short active regions on the surface’ [Computer software]. Zenodo https://doi.org/10.5281/zenodo.21722814 (2026).