Heterochromatin drives compartmentalization of inverted and conventional nuclei
Open accessAbstract
The nucleus of mammalian cells displays a distinct spatial segregation of active euchromatic and inactive heterochromatic regions of the genome 1,2. In conventional nuclei, microscopy shows that euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery 1,2. Genome-wide chromosome conformation capture (Hi-C) analyses show this segregation as a plaid pattern of contact enrichment within euchromatin and heterochromatin compartments 3, and depletion between them. Many mechanisms for the formation of compartments have been proposed, such as attraction of heterochromatin to the nuclear lamina 2,4, preferential attraction of similar chromatin to each other 1,4-12, higher levels of chromatin mobility in active chromatin 13-15 and transcription-related clustering of euchromatin 16,17. However, these hypotheses have remained inconclusive, owing to the difficulty of disentangling intra-chromatin and chromatin-lamina interactions in conventional nuclei 18. The marked reorganization of interphase chromosomes in the inverted nuclei of rods in nocturnal mammals 19,20 provides an opportunity to elucidate the mechanisms that underlie spatial compartmentalization. Here we combine Hi-C analysis of inverted rod nuclei with microscopy and polymer simulations. We find that attractions between heterochromatic regions are crucial for establishing both compartmentalization and the concentric shells of pericentromeric heterochromatin, facultative heterochromatin and euchromatin in the inverted nucleus. When interactions between heterochromatin and the lamina are added, the same model recreates the conventional nuclear organization. In addition, our models allow us to rule out mechanisms of compartmentalization that involve strong euchromatin interactions. Together, our experiments and modelling suggest that attractions between heterochromatic regions are essential for the phase separation of the active and inactive genome in inverted and conventional nuclei, whereas interactions of the chromatin with the lamina are necessary to build the conventional architecture from these segregated phases.
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Despite the disruption of Lamin B1, the A/B compartmentalization of the genome remained relatively unaffected.
“Despite the disruption of Lamin B1, the A/B compartmentalization of the genome remained relatively unaffected which is in concordance with the observations in retinal rod neurons, where despite the loss of heterochromatin interactions with the nuclear lamina, phase separation drives the formation of A/B compartments135.”
From Neuronal DNA double-strand breaks lead to genome structural variations and 3D genome disruption in neurodegeneration (2023) · cites this paper as [135]
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Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · see citing works
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212 · see citing works
Topological domains in mammalian genomes identified by analysis of chromatin interactions
Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J. S., & Ren, B. (2012) · Nature · doi:10.1038/nature11082 · Cited by 6,829 · see citing works
Rubinstein, M., & Colby, R. H. (2003) · doi:10.1093/oso/9780198520597.001.0001 · Cited by 5,686 · see citing works
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247 · see citing works
OpenMM 7: Rapid development of high performance algorithms for molecular dynamics
Eastman, P., Swails, J., Chodera, J. D., McGibbon, R. T., Zhao, Y., Beauchamp, K. A., Wang, L.-P., Simmonett, A. C., Harrigan, M. P., Stern, C. D., et al. (2017) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1005659 · Cited by 2,748 · see citing works
HiGlass: web-based visual exploration and analysis of genome interaction maps
Kerpedjiev, P., Abdennur, N. A., Lekschas, F., McCallum, C., Dinkla, K., Strobelt, H., Luber, J. M., Ouellette, S., Azhir, A., Kumar, N., et al. (2018) · Genome biology · doi:10.1186/s13059-018-1486-1 · Cited by 2,416 · see citing works
Phase separation drives heterochromatin domain formation
Strom, A. R., Emelyanov, A. V., Mir, M., Fyodorov, D. V., Darzacq, X., & Karpen, G. H. (2017) · Nature · doi:10.1038/nature22989 · Cited by 1,813 · see citing works
Cooler: scalable storage for Hi-C data and other genomically labeled arrays
Abdennur, N., & Mirny, L. A. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btz540 · Cited by 1,759 · see citing works
Nora, E. P., Goloborodko, A., Valton, A.-L., Gibcus, J. H., Uebersohn, A., Abdennur, N., Dekker, J., Mirny, L. A., & Bruneau, B. G. (2017) · Cell · doi:10.1016/j.cell.2017.05.004 · Cited by 1,709 · see citing works
Self-citationLiquid droplet formation by HP1α suggests a role for phase separation in heterochromatin
Larson, A. G., Elnatan, D., Keenen, M. M., Trnka, M., Johnston, J. B., Burlingame, A., Agard, D., Redding, S., & Narlikar, G. J. (2017) · Nature · doi:10.1038/nature22822 · Cited by 1,554 · see citing works
Iterative correction of Hi-C data reveals hallmarks of chromosome organization
Imakaev, M., Fudenberg, G., McCord, R. P., Naumova, N., Goloborodko, A., Lajoie, B. R., Dekker, J., & Mirny, L. A. (2012) · Nature Methods · doi:10.1038/nmeth.2148 · Cited by 1,423 · see citing works
Two independent modes of chromatin organization revealed by cohesin removal
Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., Loe-Mie, Y., Fonseca, N. A., Huber, W., Haering, C. H., Mirny, L., et al. (2017) · Nature · doi:10.1038/nature24281 · Cited by 1,196 · see citing works
Self-citationOrganization and function of the 3D genome
Bonev, B., & Cavalli, G. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.112 · Cited by 1,174 · see citing works
Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression
van Steensel, B., & Belmont, A. S. (2017) · Cell · doi:10.1016/j.cell.2017.04.022 · Cited by 1,140 · see citing works
Organization of the mitotic chromosome
Naumova, N., Imakaev, M., Fudenberg, G., Zhan, Y., Lajoie, B. R., Mirny, L. A., & Dekker, J. (2013) · Science · doi:10.1126/science.1236083 · Cited by 976 · see citing works
Condensin-driven remodelling of X chromosome topology during dosage compensation
Crane, E. E., Bian, Q., McCord, R. P., Lajoie, B. R., Wheeler, B. S., Ralston, E. J., Uzawa, S., Dekker, J., & Meyer, B. J. (2015) · Nature · doi:10.1038/nature14450 · Cited by 972 · see citing works
ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells
Ou, H. D., Phan, S., Deerinck, T. J., Thor, A., Ellisman, M. H., & O’Shea, C. C. (2017) · Science · doi:10.1126/science.aag0025 · Cited by 872 · see citing works
3D structures of individual mammalian genomes studied by single-cell Hi-C
Stevens, T. J., Lando, D., Basu, S., Atkinson, L. P., Cao, Y., Lee, S. F., Leeb, M., Wohlfahrt, K. J., Boucher, W., O’Shaughnessy-Kirwan, A., et al. (2017) · Nature · doi:10.1038/nature21429 · Cited by 832 · see citing works
Solovei, I., Wang, A. S., Thanisch, K., Schmidt, C. S., Krebs, S., Zwerger, M., Cohen, T. V., Devys, D., Foisner, R., Peichl, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.009 · Cited by 809 · see citing works
Nuclear Architecture of Rod Photoreceptor Cells Adapts to Vision in Mammalian Evolution
Solovei, I. V., Kreysing, M., Lanctôt, C., Kösem, S., Peichl, L., Cremer, T. J., Guck, J. R., & Joffe, B. I. (2009) · Cell · doi:10.1016/j.cell.2009.01.052 · Cited by 785 · see citing works
Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition
Flyamer, I. M., Gassler, J., Imakaev, M., Brandão, H. B., Ulianov, S. V., Abdennur, N., Razin, S. V., Mirny, L. A., & Tachibana-Konwalski, K. (2017) · Nature · doi:10.1038/nature21711 · Cited by 753 · see citing works
Eastman, P., Friedrichs, M., Chodera, J., Radmer, R. J., Bruns, C. M., Ku, J. P., Beauchamp, K., Lane, T., Wang, L.-P., Shukla, D., et al. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300857j · Cited by 678 · see citing works
Chromatin organization by an interplay of loop extrusion and compartmental segregation
Nuebler, J., Fudenberg, G., Imakaev, M., Abdennur, N. A., & Mirny, L. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717730115 · Cited by 616 · see citing works
Schmidt, D., Schwalie, P. C., Wilson, M. D., Ballester, B., Gonçalves, Â., Kutter, C., Brown, G. D., Marshall, A., Flicek, P., & Odom, D. T. (2012) · Cell · doi:10.1016/j.cell.2011.11.058 · Cited by 598 · see citing works
Spatial Organization of the Mouse Genome and Its Role in Recurrent Chromosomal Translocations
Zhang, Y., McCord, R. P., Ho, Y.-J., Lajoie, B. R., Hildebrand, D. G., Simon, A. C., Becker, M. S., Alt, F. W., & Dekker, J. (2012) · Cell · doi:10.1016/j.cell.2012.02.002 · Cited by 553 · see citing works
Structure and Dynamics of Interphase Chromosomes
Rosa, A., & Everaers, R. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000153 · Cited by 511 · see citing works
Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains
Jost, D., Carrivain, P., Cavalli, G., & Vaillant, C. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku698 · Cited by 425 · see citing works
Transferable model for chromosome architecture
Pierro, M. D., Zhang, B., Aiden, E. L., Wolynes, P. G., & Onuchic, J. N. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613607113 · Cited by 332 · see citing works
Lin, Y. C., Benner, C., Mansson, R., Heinz, S., Miyazaki, K., Miyazaki, M., Chandra, V., Bossen, C., Glass, C. K., & Murre, C. (2012) · Nature Immunology · doi:10.1038/ni.2432 · Cited by 281 · see citing works
Structural Basis of Heterochromatin Formation by Human HP1
Machida, S., Takizawa, Y., Ishimaru, M., Sugita, Y., Sekine, S., Nakayama, J., Wolf, M., & Kurumizaka, H. (2018) · Molecular Cell · doi:10.1016/j.molcel.2017.12.011 · Cited by 275 · see citing works
Lamins Organize the Global Three-Dimensional Genome from the Nuclear Periphery
Zheng, X., Hu, J., Yue, S., Kristiani, L., Kim, M., Sauria, M. E. G., Taylor, J., Kim, Y., & Zheng, Y. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.05.017 · Cited by 239 · see citing works
How to rule the nucleus: divide et impera
Solovei, I. V., Thanisch, K., & Feodorova, Y. N. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.02.014 · Cited by 183 · see citing works
Multicolor 3D Fluorescence In Situ Hybridization for Imaging Interphase Chromosomes
Cremer, M., Grasser, F., Lanctôt, C., Müller, S., Neusser, M., Zinner, R., Solovei, I. V., & Cremer, T. J. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-406-3_15 · Cited by 180 · see citing works
Nonequilibrium statistical mechanics of mixtures of particles in contact with different thermostats
Grosberg, A. Y., & Joanny, J. (2015) · Physical Review E · doi:10.1103/physreve.92.032118 · Cited by 173 · see citing works
Helmlinger, D., Hardy, S., Sleymane, G. A., Eberlin, A., Bowman, A. B., Gansmüller, A., Picaud, S. A., Zoghbi, H. Y., Trottier, Y., Tora, L., et al. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040067 · Cited by 165 · see citing works
Chromosome positioning from activity-based segregation
Ganai, N., Sengupta, S., & Menon, G. I. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1417 · Cited by 153 · see citing works
Shultz, L. D. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg003 · Cited by 136 · see citing works
Small Activity Differences Drive Phase Separation in Active-Passive Polymer Mixtures
Smrek, J., & Kremer, K. (2017) · Physical Review Letters · doi:10.1103/physrevlett.118.098002 · Cited by 128 · see citing works
Three-dimensional genome structures of single sensory neurons in mouse visual and olfactory systems
Tan, L., Xing, D., Daley, N., & Xie, X. S. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0205-2 · Cited by 115 · see citing works
Choo, K. H. A. (1997) · doi:10.1093/oso/9780198577812.001.0001 · Cited by 109 · see citing works
In Vivo Chromatin Organization of Mouse Rod Photoreceptors Correlates with Histone Modifications
Kizilyaprak, C., Spehner, D., Devys, D., & Schultz, P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011039 · Cited by 73 · see citing works
Epigenetics of eu- and heterochromatin in inverted and conventional nuclei from mouse retina
Eberhart, A., Feodorova, Y. N., Song, C., Wanner, G., Владимировна, К. Е., Furukawa, T., Kimurâ, H., Schotta, G., Leonhardt, H., Joffe, B. I., et al. (2013) · Chromosome Research · doi:10.1007/s10577-013-9375-7 · Cited by 73 · see citing works
Towards many colors in FISH on 3D-preserved interphase nuclei
Walter, J. K., Joffe, B. I., Bolzer, A., Albiez, H., Benedetti, P. A., Müller, S., Speicher, M. R., Cremer, T. J., Cremer, M., & Solovei, I. V. (2006) · Cytogenetic and Genome Research · doi:10.1159/000094227 · Cited by 72 · see citing works
Cohen, T. V., Klarmann, K. D., Sakchaisri, K., Cooper, J. P., Kuhns, D. B., Anver, M. R., Johnson, P. F., Williams, S. C., Keller, J. R., & Stewart, C. L. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn191 · Cited by 61 · see citing works
Cooler: scalable storage for Hi-C data and other genomically-labeled arraysPreprint
Abdennur, N. A., & Mirny, L. A. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/557660 · Cited by 61 · see citing works
Self-citationFeodorova, Y. N., Koch, M., Bultmann, S., Michalakis, S., & Solovei, I. V. (2015) · MethodsX · doi:10.1016/j.mex.2015.01.002 · Cited by 49 · see citing works
Small chromosomal regions position themselves autonomously according to their chromatin classPreprint
van de Werken, H. J. G., Haan, J. C., Feodorova, Y., Bijos, D. A., Weuts, A., Theunis, K., Holwerda, S. J. B., Meuleman, W. R. A., Pagie, L., Thanisch, K., et al. (2017) · Genome Research · doi:10.1101/gr.213751.116 · Cited by 43 · see citing works
HiGlass: Web-based Visual Exploration and Analysis of Genome Interaction MapsPreprint
Kerpedjiev, P., Abdennur, N. A., Lekschas, F., McCallum, C., Dinkla, K., Strobelt, H., Luber, J. M., Ouellette, S., Azhir, A., Kumar, N., et al. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/121889 · Cited by 43 · see citing works
Self-citationBiggs, R. J., Liu, P. Z., Stephens, A. D., & Marko, J. F. (2019) · Molecular Biology of the Cell · doi:10.1091/mbc.e18-09-0592 · Cited by 41 · see citing works
Chromatin organization by an interplay of loop extrusion and compartmental segregationPreprint
Nuebler, J., Fudenberg, G., Imakaev, M., Abdennur, N. A., & Mirny, L. A. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/196261 · Cited by 37 · see citing works
Self-citationTang, S. (2011) · Genes · doi:10.3390/genes2030502 · Cited by 35 · see citing works
Fluorescence in situ Hybridization (FISH) on Tissue Cryosections
Solovei, I. V. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-789-1_5 · Cited by 29 · see citing works
Reliable detection of epigenetic histone marks and nuclear proteins in tissue cryosections
Eberhart, A., Kimura, H., Leonhardt, H., Joffe, B., & Solovei, I. (2012) · Chromosome Research · doi:10.1007/s10577-012-9318-8 · Cited by 29 · see citing works
Transcription organizes euchromatin similar to an active microemulsionPreprint
Hilbert, L., Sato, Y., Kimurâ, H., Jülicher, F., Honigmann, A., Zaburdaev, V., & Vastenhouw, N. L. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/234112 · Cited by 29 · see citing works
Lee, S. S., Tashiro, S., Awazu, A., & Kobayashi, R. (2016) · Journal of Mathematical Biology · doi:10.1007/s00285-016-1031-3 · Cited by 25 · see citing works
Jerabek, H., & Heermann, D. W. (2014) · International review of cytology · doi:10.1016/b978-0-12-800046-5.00010-2 · Cited by 25 · see citing works
Flagged first, then by citations
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Sorted by citations
Histone post-translational modifications - cause and consequence of genome function
Millán-Zambrano, G., Burton, A., Bannister, A. J., & Schneider, R. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-022-00468-7 · Cited by 1,116 · see citing works
Organization of Chromatin by Intrinsic and Regulated Phase Separation
Gibson, B. A., Doolittle, L. K., Schneider, M. W. G., Jensen, L. E., Gamarra, N. I., Henry, L., Gerlich, D. W., Redding, S., & Rosen, M. K. (2019) · Cell · doi:10.1016/j.cell.2019.08.037 · Cited by 1,045 · see citing works
“Consistent with this conceptual framework, recent efforts to recapitulate whole-genome chromatin interaction maps in silico have invoked phase separation, driven by weak but differential interactions of chromatin and associated factors, to account for the formation and segregation of chromatin sub-domains (Di Pierro e…”
BackgroundThe Self-Organizing Genome: Principles of Genome Architecture and Function
Misteli, T. (2020) · Cell · doi:10.1016/j.cell.2020.09.014 · Cited by 705 · see citing works
“, 2018) and the observed inversion of heterochromatin towards the nuclear interior in retinal rod cells (Falk et al., 2019), can only be recreated by including phase separation in polymer-based modeling approaches.”
Ultrastructural Details of Mammalian Chromosome Architecture
Krietenstein, N., Abraham, S., Venev, S. V., Abdennur, N., Gibcus, J., Hsieh, T.-H. S., Parsi, K. M., Yang, L., Maehr, R., Mirny, L. A., et al. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.003 · Cited by 622 · see citing works
Self-citationGenome-Scale Imaging of the 3D Organization and Transcriptional Activity of Chromatin
Su, J.-H., Zheng, P., Kinrot, S. S., Bintu, B., & Zhuang, X. (2020) · Cell · doi:10.1016/j.cell.2020.07.032 · Cited by 562 · see citing works
“This average picture is consistent with the hierarchy of A and B chromatin interaction strengths suggested based on Hi-C and imaging data (Falk et al., 2019).”
Integrated spatial genomics reveals global architecture of single nuclei
Takei, Y., Yun, J., Zheng, S., Ollikainen, N., Pierson, N. G., White, J. A., Shah, S., Thomassie, J., Suo, S., Eng, C.-H. L., et al. (2021) · Nature · doi:10.1038/s41586-020-03126-2 · Cited by 399 · see citing works
Modulating biomolecular condensates: a novel approach to drug discovery
Mitrea, D. M., Mittasch, M., Gomes, B. F., Klein, I. A., & Murcko, M. A. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00505-4 · Cited by 408 · see citing works
Understanding 3D genome organization by multidisciplinary methods
Jerković, I., & Cavalli, G. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00362-w · Cited by 388 · see citing works
Capillary forces generated by biomolecular condensates
Gouveia, B., Kim, Y., Shaevitz, J. W., Petry, S., Stone, H. A., & Brangwynne, C. P. (2022) · Nature · doi:10.1038/s41586-022-05138-6 · Cited by 275 · see citing works
3D genomics across the tree of life reveals condensin II as a determinant of architecture type
Hoencamp, C., Dudchenko, O., Elbatsh, A. M. O., Brahmachari, S., Raaijmakers, J. A., van Schaik, T., Cacciatore, Á. S., Contessoto, V. G., van Heesbeen, R. G. H. P., van den Broek, B., et al. (2021) · Science · doi:10.1126/science.abe2218 · Cited by 262 · see citing works
Mechanisms and Functions of Chromosome Compartmentalization
Hildebrand, E. M., & Dekker, J. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.01.002 · Cited by 268 · see citing works
“compartment formation, which, in the future, can be compared to forces that can be exerted through the different microphase separation mechanisms [66].”
BackgroundMethodResultInfluentialLamina-associated domains: peripheral matters and internal affairs
Briand, N., & Collas, P. (2020) · Genome biology · doi:10.1186/s13059-020-02003-5 · Cited by 269 · see citing works
Transcription in Living Cells: Molecular Mechanisms of Bursting
Rodriguez, J., & Larson, D. R. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-011520-105250 · Cited by 224 · see citing works
The liquid nucleome – phase transitions in the nucleus at a glance
Strom, A. R., & Brangwynne, C. P. (2019) · Journal of Cell Science · doi:10.1242/jcs.235093 · Cited by 223 · see citing works
“Such large-scale localization changes (inversion) of heterochromatin reorganize the chromatin fiber on the nuclear scale (Falk et al., 2019).”
BackgroundHomotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome
Lu, J. Y., Chang, L., Li, T., Wang, T., Yin, Y., Zhan, G., Han, X., Zhang, K., Tao, Y., Percharde, M., et al. (2021) · Cell Research · doi:10.1038/s41422-020-00466-6 · Cited by 205 · see citing works
“Together with the Solovei group, they further proposed that interactions between heterochromatic regions, rather than euchromatic contacts and lamina-heterochromatin interactions, are crucial for compartmentalization of the genome in both inverted and conventional nuclei.(29,34) However, what was unknown in their mode…”
BackgroundLarge-Scale Topological Changes Restrain Malignant Progression in Colorectal Cancer
Johnstone, S. E., Reyes, A., Qi, Y., Adriaens, C., Hegazi, E., Pelka, K., Chen, J. H., Zou, L. S., Drier, Y., Hecht, V. C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.07.030 · Cited by 215 · see citing works
Molecular basis of CTCF binding polarity in genome folding
Nora, E. P., Caccianini, L., Fudenberg, G., So, K., Kameswaran, V., Nagle, A., Uebersohn, A., Hajj, B., Saux, A. L., Coulon, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19283-x · Cited by 206 · see citing works
A chromosome folding intermediate at the condensin-to-cohesin transition during telophase
Abramo, K., Valton, A.-L., Venev, S. V., Özadam, H., Fox, A. N., & Dekker, J. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0406-2 · Cited by 196 · see citing works
McCord, R. P., Kaplan, N., & Giorgetti, L. (2020) · Molecular Cell · doi:10.1016/j.molcel.2019.12.021 · Cited by 204 · see citing works
“2009) which appear to be formed by attractive interactions of unclear origin, but possibly mediated by mechanisms involving phase separation of chromatin-associated proteins (Wang et al. 2019b; Strom et al. 2017; Sanulli et al. 2015; Strom et al. 2017; Falk et al. 2019), (Figure 1C).”
BackgroundIn situ genome sequencing resolves DNA sequence and structure in intact biological samples
Payne, A. C., Chiang, Z., Reginato, P., Mangiameli, S. M., Murray, E. M., Yao, C., Markoulaki, S., Earl, A., Labade, A. S., Jaenisch, R., et al. (2021) · Science · doi:10.1126/science.aay3446 · Cited by 198 · see citing works
“Given our observations of radial patterns of chromosome positioning and the known radial organization of heterochromatin (41), we investigated whether repetitive elements displayed radial patterns.”
BackgroundPoudyal, M., Patel, K., Gadhe, L. G., Sawner, A. S., Kadu, P., Datta, D., Mukherjee, S., Ray, S., Navalkar, A., Maiti, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41864-9 · Cited by 194 · see citing works
Biological phase separation: cell biology meets biophysics
Yoshizawa, T., Nozawa, R., Jia, T. Z., Saio, T., & Mori, E. (2020) · Biophysical Reviews · doi:10.1007/s12551-020-00680-x · Cited by 188 · see citing works
“A disordered region of proteins termed the intrinsically disordered region (IDR), or the low-complexity (LC) domain, facilitates assembly (Kato et al. 2012; Forman-Kay and Mittag 2013; Nott et al. 2015).”
BackgroundChromatin alternates between A and B compartments at kilobase scale for subgenic organization
Harris, H. L., Gu, H., Olshansky, M., Wang, A., Farabella, I., Eliaz, Y., Kalluchi, A., Krishna, A., Jacobs, M., Cauer, G., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38429-1 · Cited by 184 · see citing works
Thiecke, M. J., Wutz, G., Muhar, M., Tang, W., Bevan, S., Malysheva, V., Stocsits, R., Neumann, T., Zuber, J., Fraser, P., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107929 · Cited by 177 · see citing works
Revealing Hi-C subcompartments by imputing inter-chromosomal chromatin interactions
Xiong, K., & Ma, J. (2019) · Nature Communications · doi:10.1038/s41467-019-12954-4 · Cited by 143 · see citing works
Modulating α-Synuclein Liquid–Liquid Phase Separation
Sawner, A. S., Ray, S., Yadav, P., Mukherjee, S., Panigrahi, R., Poudyal, M., Patel, K., Ghosh, D., Kummerant, E., Kumar, A., et al. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00434 · Cited by 148 · see citing works
Chromatin accessibility: methods, mechanisms, and biological insights
Mansisidor, A., & Risca, V. I. (2022) · Nucleus · doi:10.1080/19491034.2022.2143106 · Cited by 150 · see citing works
“Transcriptional repression and compartmentalization are maintained by redundant mechanisms, and individual perturbations, including ones as dramatic as partially inverting the spatial organization of heterochromatin in the nucleus by knocking out the lamin B receptor, did not change the compartment map measurable by H…”
BackgroundInfluentialExtracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells
Mierke, C. T. (2024) · Cells · doi:10.3390/cells13010096 · Cited by 146 · see citing works
Huo, X., Ji, L., Zhang, Y., Lv, P., Cao, X. D., Wang, Q., Yan, Z., Dong, S., Du, D., Zhang, F., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.10.001 · Cited by 143 · see citing works
Genome control by SMC complexes
Hoencamp, C., & Rowland, B. D. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00609-8 · Cited by 138 · see citing works
Transcription organizes euchromatin via microphase separation
Hilbert, L., Sato, Y., Kuznetsova, K., Bianucci, T., Kimurâ, H., Jülicher, F., Honigmann, A., Zaburdaev, V., & Vastenhouw, N. L. (2021) · Nature Communications · doi:10.1038/s41467-021-21589-3 · Cited by 144 · see citing works
Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers
Spracklin, G., Abdennur, N. A., Imakaev, M., Chowdhury, N., Pradhan, S., Mirny, L. A., & Dekker, J. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00892-7 · Cited by 139 · see citing works
Liquid chromatin Hi-C characterizes compartment-dependent chromatin interaction dynamics
Belaghzal, H., Borrman, T. M., Stephens, A. D., Lafontaine, D. L. J., Venev, S. V., Weng, Z., Marko, J. F., & Dekker, J. (2021) · Nature Genetics · doi:10.1038/s41588-021-00784-4 · Cited by 132 · see citing works
HP1 drives de novo 3D genome reorganization in early Drosophila embryos
Zenk, F. L., Zhan, Y., Kos, P. I., Löser, E., Atinbayeva, N., Schächtle, M., Tiana, G., Giorgetti, L., & Iovino, N. (2021) · Nature · doi:10.1038/s41586-021-03460-z · Cited by 128 · see citing works
Ulianov, S. V., Velichko, A. K., Magnitov, M. D., Luzhin, A. V., Golov, A. K., Ovsyannikova, N., Kireev, I. I., Gavrikov, A. S., Mishin, A. S., Garaev, A. K., et al. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab249 · Cited by 137 · see citing works
“We next separately analyzed the compartment strength (Falk et al. 2019) in the Control, Hex5, and Recovery matrices for cis- and trans-interactions.”
MethodInfluentialDileep, V., Boix, C. A., Mathys, H., Marco, A., Welch, G. M., Meharena, H. S., Loon, A., Jeloka, R., Peng, Z., Bennett, D. A., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.038 · Cited by 130 · see citing works
“133 Changes in the 3D genome aligned with transcriptional cha-nges overall, with reduced loop intensities having a striking correlation with the down-regulation of genes.”
BackgroundThe chromosome folding problem and how cells solve it
Dekker, J., & Mirny, L. A. (2024) · Cell · doi:10.1016/j.cell.2024.10.026 · Cited by 112 · see citing works
SPIN reveals genome-wide landscape of nuclear compartmentalization
Wang, Y., Zhang, Y., Zhang, R., van Schaik, T., Zhang, L., Sasaki, T., Peric‐Hupkes, D., Chen, Y., Gilbert, D. M., van Steensel, B., et al. (2021) · Genome biology · doi:10.1186/s13059-020-02253-3 · Cited by 114 · see citing works
Functional mechanisms and abnormalities of the nuclear lamina
Karoutas, A., & Akhtar, A. (2021) · Nature Cell Biology · doi:10.1038/s41556-020-00630-5 · Cited by 116 · see citing works
Liu, Y., Nanni, L., Sungalee, S., Zufferey, M., Tavernari, D., Mina, M., Ceri, S., Oricchio, E., & Ciriello, G. (2021) · Nature Communications · doi:10.1038/s41467-021-22666-3 · Cited by 112 · see citing works
“Loop extrusion has been associated with the formation of topologically associating domains (TADs) and structural loops 8 – 10 , whereas chromatin compartmentalization segregates the chromatin into spatial compartments 11,12 and compartment domains 10 .”
BackgroundThe NSL complex maintains nuclear architecture stability via lamin A/C acetylation
Karoutas, A., Szymanski, W. G., Rausch, T., Guhathakurta, S., Rog‐Zielinska, E. A., Peyronnet, R., Seyfferth, J., Chen, H., de Leeuw, R., Herquel, B., et al. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0397-z · Cited by 113 · see citing works
Multiplexed imaging of nucleome architectures in single cells of mammalian tissue
Liu, M., Lu, Y., Yang, B., Chen, Y., Radda, J. S. D., Hu, M., Katz, S. G., & Wang, S. S. (2020) · Nature Communications · doi:10.1038/s41467-020-16732-5 · Cited by 106 · see citing works
Rebooting the Epigenomes during Mammalian Early Embryogenesis
Xia, W., & Xie, W. (2020) · Stem Cell Reports · doi:10.1016/j.stemcr.2020.09.005 · Cited by 111 · see citing works
“Chromatin compartmentalization is believed to be driven by phase separation of chromatin with similar physical states (Falk et al., 2019).”
BackgroundMechanisms of Chromosome Folding and Nuclear Organization: Their Interplay and Open QuestionsPreprint
Mirny, L. A., & Dekker, J. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040147 · Cited by 102 · see citing works
Chang, L., Li, M., Shao, S., Li, C., Ai, S., Xue, B., Hou, Y., Zhang, Y., Li, R., Fan, X., et al. (2020) · Protein & Cell · doi:10.1007/s13238-020-00794-8 · Cited by 113 · see citing works
“developed a polymer model of chromosomes to reconstruct chromatin subnuclear localization in inverted and conventional nuclei (Falk et al., 2019).”
BackgroundClose to the edge: Heterochromatin at the nucleolar and nuclear peripheries
Bizhanova, A., & Kaufman, P. D. (2020) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2020.194666 · Cited by 107 · see citing works
“This is in agreement with the hypothesis that stable interactions in heterochromatin drive the A-B compartmentalization [16].”
BackgroundResultInfluentialReciprocal regulation of cellular mechanics and metabolism
Evers, T. M. J., Holt, L. J., Alberti, S., & Mashaghi, A. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00384-w · Cited by 103 · see citing works
CTCF as a boundary factor for cohesin-mediated loop extrusion: evidence for a multi-step mechanism
Hansen, A. (2020) · The Nucleus · doi:10.1080/19491034.2020.1782024 · Cited by 90 · see citing works
“In fact, polymers of distinct A/B segments, known as block copolymers, naturally undergo microphase separation [3,12,15].”
BackgroundDesign principles of 3D epigenetic memory systems
Owen, J. A., Osmanović, D., & Mirny, L. A. (2023) · Science · doi:10.1126/science.adg3053 · Cited by 104 · see citing works
Smrek, J., Chubak, I., Likos, C. N., & Kremer, K. (2020) · Nature Communications · doi:10.1038/s41467-019-13696-z · Cited by 102 · see citing works
Cremer, T., Cremer, M., Hübner, B., Silahtaroglu, A., Hendzel, M. J., Lanctôt, C., Strickfaden, H., & Cremer, C. G. (2020) · BioEssays · doi:10.1002/bies.201900132 · Cited by 101 · see citing works
Zhang, X., Liu, X., Du, Z., Wei, L., Fang, H., Dong, Q., Niu, J., Li, Y., Gao, J. T., Zhang, M. Q., et al. (2021) · Genome Research · doi:10.1101/gr.275235.121 · Cited by 101 · see citing works
Phase separation in genome organization across evolution
Feric, M., & Misteli, T. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.03.001 · Cited by 100 · see citing works
Principles of 3D compartmentalization of the human genome
Nichols, M. H., & Corces, V. G. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109330 · Cited by 99 · see citing works
“Other studies have also successfully used polymer simulations to reproduce the compartmental organization of the genome using chromatin-defined states (Annunziatella et al., 2018; Buckle et al., 2018; Chiang et al., 2019; Cook and Marenduzzo, 2018; Falk et al., 2019; Nuebler et al., 2018; Qi and Zhang, 2019).”
BackgroundMethodHi-D: nanoscale mapping of nuclear dynamics in single living cells
Shaban, H. A., Barth, R., Recoules, L., & Bystricky, K. (2020) · Genome biology · doi:10.1186/s13059-020-02002-6 · Cited by 97 · see citing works
Xue, L., Gao, Y., Wu, M., Tian, T., Fan, H., Huang, Y., Huang, Z. J., Li, D., & Xu, L. (2021) · Genome biology · doi:10.1186/s13059-021-02430-y · Cited by 96 · see citing works
“How PCH impacts 3D genome organization [48] in fish is a subject of future study.”
BackgroundTime-dependent effect of 1,6-hexanediol on biomolecular condensates and 3D chromatin organization
Liu, X., Jiang, S., Ma, L., Qu, J., Zhao, L., Zhu, X. Q., & Ding, J. (2021) · Genome biology · doi:10.1186/s13059-021-02455-3 · Cited by 95 · see citing works
Spatial multi-omics reveals cell-type-specific nuclear compartments
Takei, Y., Yang, Y., White, J. A., Goronzy, I. N., Yun, J., Prasad, M., Ombelets, L. J., Schindler, S., Bhat, P., Guttman, M., et al. (2025) · Nature · doi:10.1038/s41586-025-08838-x · Cited by 98 · see citing works
Computational methods for analysing multiscale 3D genome organization
Zhang, Y., Boninsegna, L., Yang, M., Misteli, T., Alber, F., & Ma, J. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00638-1 · Cited by 90 · see citing works
The Nuclear LaminaPreprint
Wong, X., Melendez-Perez, A. J., & Reddy, K. L. (2021) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a040113 · Cited by 92 · see citing works
DNA methylation dynamics at transposable elements in mammals
Jansz, N. (2019) · Essays in Biochemistry · doi:10.1042/ebc20190039 · Cited by 89 · see citing works
Chromatin Hyperacetylation Impacts Chromosome Folding by Forming a Nuclear Subcompartment
Rosencrance, C. D., Ammouri, H., Yu, Q., Ge, T., Rendleman, E. J., Marshall, S. A., & Eagen, K. P. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.03.018 · Cited by 87 · see citing works
“Large-scale chromosome folding over many megabases must reflect an undetermined, cohesin-independent folding mechanism (Eagen, 2018; Falk et al., 2019; Nuebler et al., 2018; Rao et al., 2017; Schwarzer et al., 2017).”
BackgroundYildirir, G., Sperschneider, J., Mathu Malar, C., Chen, E. C., Iwasaki, W., Cornell, C., & Corradi, N. (2021) · New Phytologist · doi:10.1111/nph.17842 · Cited by 89 · see citing works
Phase separation in transcription factor dynamics and chromatin organization
Wagh, K., Garcia, D. A., & Upadhyaya, A. (2021) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2021.06.009 · Cited by 86 · see citing works
Heterochromatin as an Important Driver of Genome Organization
Penagos‐Puig, A., & Furlan-Magaril, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.579137 · Cited by 80 · see citing works
Polymer Modeling Predicts Chromosome Reorganization in Senescence
Chiang, M., Michieletto, D., Brackley, C. A., Rattanavirotkul, N., Mohammed, H., Marenduzzo, D., & Chandra, T. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.045 · Cited by 77 · see citing works
“In the rod cells of nocturnal mammals, HC also detaches from the lamina but forms a single, larger aggregate (Falk et al., 2019).”
BackgroundMethodMechanistic modeling of chromatin folding to understand function
Brackley, C. A., Marenduzzo, D., & Gilbert, N. (2020) · Nature Methods · doi:10.1038/s41592-020-0852-6 · Cited by 80 · see citing works
Architecture and Dynamics of Meiotic Chromosomes
Ur, S. N., & Corbett, K. D. (2021) · Annual Review of Genetics · doi:10.1146/annurev-genet-071719-020235 · Cited by 82 · see citing works
Transcriptional enhancers and their communication with gene promoters
Ray-Jones, H., & Spivakov, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03903-w · Cited by 81 · see citing works
“It has been suggested that A/B compartments may be facilitated by affinity of heterochromatin regions to each other [460, 461].”
BackgroundMulti-contact 3C reveals that the human genome during interphase is largely not entangled
Tavares-Cadete, F., Norouzi, D., Dekker, B., Liu, Y., & Dekker, J. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0506-5 · Cited by 78 · see citing works
RNA polymerase II clusters form in line with surface condensation on regulatory chromatin
Pancholi, A., Klingberg, T., Zhang, W., Prizak, R., Mamontova, I., Noa, A., Sobucki, M., Kobitski, A. Y., Nienhaus, G. U., Zaburdaev, V., et al. (2021) · Molecular Systems Biology · doi:10.15252/msb.202110272 · Cited by 83 · see citing works
“Complex morphologies of phaseseparated droplets can also occur in multi-component condensates (Feric et al, 2016).”
BackgroundCondensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity
Strom, A. R., Kim, Y., Zhao, H., Chang, Y.-C., Orlovsky, N. D., Košmrlj, A., Storm, C., & Brangwynne, C. P. (2024) · Cell · doi:10.1016/j.cell.2024.07.034 · Cited by 79 · see citing works
“14 Aberrant spatiotemporal regulation of chromatin-interacting condensates is associated with diseased states.”
Epigenetic Regulation of Inflammatory Signaling and Inflammation-Induced Cancer
Tan, S. Y. X., Zhang, J., & Tee, W. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.931493 · Cited by 83 · see citing works
“Nuclear Substructures and Chromosome Territories On top of genomic macro-domains like TADs and A/B compartments, heterochromatinization engenders the 3D nuclear structure (Falk et al., 2019), which consists of regions associated with the nucleolus and nuclear lamina, including pericentric heterochromatin (Guenatri et…”
BackgroundSungalee, S., Liu, Y., Lambuta, R. A., Katanayeva, N., Donaldson Collier, M., Tavernari, D., Roulland, S., Ciriello, G., & Oricchio, E. (2021) · Nature Genetics · doi:10.1038/s41588-021-00842-x · Cited by 70 · see citing works
Bian, Q., Anderson, E. C., Yang, Q., & Meyer, B. J. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2002068117 · Cited by 69 · see citing works
“In a recent simulation study, the compartment organization observed in mammalian cells was best explained by a model in which interactions among heterochromatic regions are energetically favorable (22).”
BackgroundMesoscale phase separation of chromatin in the nucleus
Bajpai, G., Pavlov, D. A., Lorber, D., Volk, T., & Safran, S. A. (2021) · eLife · doi:10.7554/elife.63976 · Cited by 77 · see citing works
Stender, E. G. P., Ray, S., Norrild, R. K., Larsen, J. A., Petersen, D., Farzadfard, A., Galvagnion, C., Jensen, H. M., & Buell, A. K. (2021) · Nature Communications · doi:10.1038/s41467-021-27433-y · Cited by 77 · see citing works
Polymer folding through active processes recreates features of genome organization
Goychuk, A., Kannan, D., Chakraborty, A. K., & Mehran Kardar, A. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2221726120 · Cited by 71 · see citing works
Generation of dynamic three-dimensional genome structure through phase separation of chromatin
Fujishiro, S., & Sasai, M. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2109838119 · Cited by 74 · see citing works
“This anomalous chromatin distribution was remedied in the models by assuming the counteracting attractive interactions between chromatin and the nuclear lamina [27, 22].”
Shah, P. P., Keough, K. C., Gjoni, K., Santini, G. T., Abdill, R. J., Wickramasinghe, N. M., Dundes, C. E., Karnay, A. M., Chen, A. C., Salomon, R. E. A., et al. (2023) · Genome biology · doi:10.1186/s13059-023-02849-5 · Cited by 74 · see citing works
“…in nuclear lamins disrupt chromatin organization and cause disease, and absence of nuclear lamins contributes to chromatin inversion (Briand et al., 2018; Falk et al., 2019; Lee et al., 2019; Shah et al., 2021; Solovei et al., 2013; Vadrot et al., 2015; Worman and Bonne, 2007; Zheng and Xie, 2019).”
BackgroundOrder and disorder: abnormal 3D chromatin organization in human disease
Anania, C., & Lupiáñez, D. G. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz028 · Cited by 69 · see citing works
“For example, studies on cells lacking the expression of lamin A/C and lamin B receptor (LBR), like nocturnal animal rods with inverted nuclei [62], show a dramatic relocation of heterochromatin from the periphery to the nuclear center [63].”
BackgroundSoft materials as biological and artificial membranes
Tang, S., Davoudi, Z., Wang, G., Xu, Z., Rehman, T. U., Promiński, A., Tian, B., Bratlie, K. M., Peng, H., & Wang, Q. (2021) · Chemical Society Reviews · doi:10.1039/d1cs00029b · Cited by 72 · see citing works
Li, J., Zhang, J., Liu, J., Zhou, Y., Cai, C., Xu, L., Dai, X.-L., Feng, S.-H., Guo, C., Rao, J., et al. (2020) · bioRxiv · doi:10.1093/gigascience/giaa142 · Cited by 43 · see citing works
Tortora, M. M. C., Brennan, L. D., Karpen, G., & Jost, D. (2023) · bioRxiv · doi:10.1073/pnas.2211855120 · Cited by 62 · see citing works
“1 C ) was representative of the formation of large chromocenters, it may be unable to describe the existing multiplicity of smaller, spatially distinct HP1 compartments (44), observed during interphase in conventional mammalian nuclei (35).”
BackgroundThe rich inner life of the cell nucleus: dynamic organization, active flows, and emergent rheology
Zidovska, A. (2020) · Biophysical Reviews · doi:10.1007/s12551-020-00761-x · Cited by 69 · see citing works
“…al. 2017), computational simulations suggested that HP1 association with parts of the chromatin fiber could lead to microphase polymer separation of heterochromatin and euchromatin in the absence of a solvent and thus without any hydrodynamic interactions (MacPherson et al. 2018; Falk et al. 2019).”
BackgroundLamina-Dependent Stretching and Unconventional Chromosome Compartments in Early C. elegans Embryos
Sawh, A. N., Shafer, M. E. R., Su, J.-H., Zhuang, X., Wang, S. S., & Mango, S. E. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.02.006 · Cited by 64 · see citing works
“B compartments also depend on the interaction of DNA with the nuclear lamina to promote and radially sequester heterochromatin in lamina-associated domains (LADs) (Falk et al., 2019; Luperchio et al., 2014; van Steensel and Belmont, 2017).”
BackgroundBRD2 compartmentalizes the accessible genome
Xie, L., Dong, P., Qi, Y., Hsieh, T.-H. S., English, B. P., Jung, S., Chen, X., Marzio, M. D., Casellas, R. C., Chang, H. Y., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01044-9 · Cited by 61 · see citing works
“pAG-Tn5 was ordered from EpiCypher (15-1017).”
Structural insights into p300 regulation and acetylation-dependent genome organisation
Ibrahim, Z., Wang, T., Destaing, O., Salvi, N., Hoghoughi, N., Chabert, C., Rusu, A., Gao, J., Feletto, L., Reynoird, N., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35375-2 · Cited by 64 · see citing works
“5c; row 10, 11, Supplementary Movie 1).”
Establishment and evolution of heterochromatin
Liu, J., Ali, M., & Zhou, Q. (2020) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14303 · Cited by 65 · see citing works
Feng, Y., Wang, Y., Wang, X., He, X., Chen, Y., Naseri, A., Pederson, T., Zheng, J., Zhang, S., Xiao, X., et al. (2020) · Genome biology · doi:10.1186/s13059-020-02201-1 · Cited by 64 · see citing works
“Heterochromatin drives compartmentalization in the inverted nuclei of rods in nocturnal mammals [10].”
BackgroundDu, Q., Smith, G. C., Luu, P., Ferguson, J. M., Armstrong, N. J., Caldon, C. E., Campbell, E. M., Nair, S. S., Zotenko, E., Gould, C. M., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109722 · Cited by 65 · see citing works
Principles and functions of pericentromeric satellite DNA clustering into chromocenters
Brändle, F., Frühbauer, B., & Jagannathan, M. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.02.005 · Cited by 63 · see citing works
Determining chromatin architecture with Micro Capture-C
Hamley, J. C., Li, H., Denny, N., Downes, D. J., & Davies, J. O. J. (2023) · Nature Protocols · doi:10.1038/s41596-023-00817-8 · Cited by 59 · see citing works
“Whereas the ‘ B ’ compartments colocalize with heterochromatin, which preferentially localizes toward the nuclear periphery in lamina-associated domains 12 .”
BackgroundData-Driven Polymer Model for Mechanistic Exploration of Diploid Genome Organization
Qi, Y., Reyes, A., Johnstone, S. E., Aryee, M. J., Bernstein, B., & Zhang, B. (2020) · Biophysical Journal · doi:10.1016/j.bpj.2020.09.009 · Cited by 58 · see citing works
Lamina-associated domains: Tethers and looseners
Manzo, S. G., Dauban, L., & van Steensel, B. (2022) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2022.01.004 · Cited by 61 · see citing works
Nuclear and genome dynamics underlying DNA double-strand break repair
Chiolo, I., Altmeyer, M., Legube, G., & Mekhail, K. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00828-1 · Cited by 65 · see citing works
“This effect is reminiscent of the behaviour of H3K9me3 heterochromatin domains, which, when detached from the nuclear lamina, coalesce into large internal heterochromatic foci that can trigger the formation of ‘inverted’ nuclei in extreme cases 210 .”
Exploring chromosomal structural heterogeneity across multiple cell lines
Cheng, R. R., Contessoto, V. G., Aiden, E. L., Wolynes, P. G., Pierro, M. D., & Onuchic, J. N. (2020) · eLife · doi:10.7554/elife.60312 · Cited by 58 · see citing works
Chromatin Conformation in Development and Disease
Boltsis, I., Grosveld, F. G., Giraud, G., & Kolovos, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.723859 · Cited by 56 · see citing works
Mesoscale structure–function relationships in mitochondrial transcriptional condensates
Feric, M., Sarfallah, A., Dar, F., Temiakov, D., Pappu, R. V., & Misteli, T. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2207303119 · Cited by 58 · see citing works
Dong, P., Tu, X., Liang, Z., Kang, B., & Zhong, S. (2020) · Journal of Experimental Botany · doi:10.1093/jxb/eraa220 · Cited by 59 · see citing works
- Authors
- Falk, M., Feodorova, Y., Naumova, N., Imakaev, M., Lajoie, B. R., Leonhardt, H., Joffe, B., Dekker, J., Fudenberg, G., Solovei, I., & Mirny, L. A.
- Affiliations
- Massachusetts Institute of Technology (US)
- Medical University Plovdiv (BG)
- Howard Hughes Medical Institute (US)
- Ludwig-Maximilians-Universität München (DE)
- Gladstone Institutes (US)
- Corresponding author
- Fudenberg, Geoffrey
- Solovei, Irina
- Mirny, Leonid A.
- ORCID
- Venue
- Nature
- Published
- 2019-06
- Volume
- 570
- Issue
- 7761
- Pages
- 395-399
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7206897
- OpenAlex
- W2948487481
- Cited by
- 646
- References
- 55
- Citations by year
- 2026: 50 · 2025: 84 · 2024: 95 · 2023: 90 · 2022: 90 · 2021: 116 · 2020: 88 · 2019: 33
- FWCI
- 28.63
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-08-02)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship@UMassChan (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Human Genome Research Institute (RM1HG007743, R01HG003143)
- National Institute of General Medical Sciences (R01GM114190)
- National Institute of Diabetes and Digestive and Kidney Diseases (U54DK107980)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- nuclear compartmentalization, heterochromatin, rod photoreceptors, nuclear lamina, euchromatin, pericentromeric heterochromatin, facultative heterochromatin, phase separation, chromosome conformation, chromatin organization, polymer simulation
- MeSH terms
- Animals, Cell Compartmentation, Cell Nucleus, Heterochromatin, Models, Biological, Time Factors, Euchromatin, Nuclear Lamina, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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