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Self-organization of domain structures by DNA-loop-extruding enzymes
Open accessAbstract
The long chromosomal DNAs of cells are organized into loop domains much larger in size than individual DNA-binding enzymes, presenting the question of how formation of such structures is controlled. We present a model for generation of defined chromosomal loops, based on molecular machines consisting of two coupled and oppositely directed motile elements which extrude loops from the double helix along which they translocate, while excluding one another sterically. If these machines do not dissociate from DNA (infinite processivity), a disordered, exponential steady-state distribution of small loops is obtained. However, if dissociation and rebinding of the machines occurs at a finite rate (finite processivity), the steady state qualitatively changes to a highly ordered 'stacked' configuration with suppressed fluctuations, organizing a single large, stable loop domain anchored by several machines. The size of the resulting domain can be simply regulated by boundary elements, which halt the progress of the extrusion machines. Possible realizations of these types of molecular machines are discussed, with a major focus on structural maintenance of chromosome complexes and also with discussion of type I restriction enzymes. This mechanism could explain the geometrically uniform folding of eukaryote mitotic chromosomes, through extrusion of pre-programmed loops and concomitant chromosome compaction.
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“this favors a linear tracking mechanism,47 known as the “loop extrusion model”.8,9,48”
From Recent evidence that TADs and chromatin loops are dynamic structures (2018) · cites this paper as [48]
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Items 101–200 of 540
TADs and Their Borders: Free Movement or Building a Wall?
Chang, L., Ghosh, S., & Noordermeer, D. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.11.025 · Cited by 97
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Ryu, J., Katan, A. J., van der Sluis, E. O., Wisse, T., de Groot, R., Haering, C. H., & Dekker, C. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0508-3 · Cited by 96
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“…of the loop extrusion process have explained a variety of observed phenomena 99,100 , including mitotic chromosome compaction and segregation 93,101–103 , meiotic chromosome organization 104 , interphase chromatin domains and loops 7,94 , and functional interactions, such as V(D)J…”
Paulson, J. R., Hudson, D. F., Cisneros-Soberanis, F., & Earnshaw, W. C. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.03.014 · Cited by 96
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“Not all these CTCF sites necessarily form loops if we assume that convergent CTCF sites are brought together by a (semi)processive extrusion-like process that will start by folding a chromatin strand on itself followed by reeling-in DNA to extend the nascent loop [14, 15, 18, 34].”
Background3D ATAC-PALM: super-resolution imaging of the accessible genome
Xie, L., Dong, P., Chen, X., Hsieh, T.-H. S., Banala, S., Marzio, M. D., English, B. P., Qi, Y., Jung, S. K., Kieffer-Kwon, K.-R., et al. (2020) · Nature Methods · doi:10.1038/s41592-020-0775-2 · Cited by 86
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“Chromosome-conformation-capture studies (Hi-C and derivatives) (7,8) and 3D polymer simulations showed that loop extrusion by condensin can efficiently generate compaction of chromatin fibers (9,10).”
DamC reveals principles of chromatin folding in vivo without crosslinking and ligation
Redolfi, J., Zhan, Y., Valdes-Quezada, C., Kryzhanovska, M., Guerreiro, I., Iesmantavicius, V., Pollex, T., Grand, R. S., Mulugeta, E., Kind, J., et al. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0231-0 · Cited by 86
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“A conceivable mechanism for lengthwise compaction is progressive “extrusion” of chromatin loops by condensins (Marko, 2011, Alipour and Marko, 2012, Marko, 2009, Nasmyth, 2001, Goloborodko et al., 2016a, Goloborodko et al., 2016b, Gibcus et al., 2018, Ganji et al., 2018).”
Self-citationWu, Q., Guo, Y., Lu, Y., Li, J., Guo, Y., & Jia, Z. (2020) · Genome biology · doi:10.1186/s13059-020-01984-7 · Cited by 84
“In the 1D lattice loop extrusion, “two heads” of the cohesin (loop-extrusion factor) independently extrude a DNA loop in opposite directions in an ATP-dependent manner until blocked by CTCF insulators asymmetrically or dropping off from the coarse-grained chromatin fiber (Additional file 1: Figure S7g) [19, 76].”
BackgroundInfluentialJpx RNA regulates CTCF anchor site selection and formation of chromosome loops
Oh, H. J., Aguilar, R., Kesner, B., Lee, H.-G., Kriz, A. J., Chu, H.-P., & Lee, J. T. (2021) · Cell · doi:10.1016/j.cell.2021.11.012 · Cited by 84
Structural basis for Scc3-dependent cohesin recruitment to chromatin
Li, Y., Muir, K., Bowler, M. W., Metz, J., Haering, C. H., & Panne, D. (2018) · eLife · doi:10.7554/elife.38356 · Cited by 84
Real‐time detection of condensin‐driven DNA compaction reveals a multistep binding mechanism
Eeftens, J., Bisht, S., Kerssemakers, J., Kschonsak, M., Haering, C., & Dekker, C. (2017) · bioRxiv · doi:10.15252/embj.201797596 · Cited by 79
“Models for the condensin-driven compaction of DNA include random cross-linking, condensin multimerization, and/or DNA loop extrusion (Alipour & Marko, 2012; Wilhelm et al , 2015; Fudenberg et al , 2016; Goloborodko et al , 2016a,b).”
Lyu, X., Rowley, M. J., & Corces, V. G. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.07.012 · Cited by 84
“To explain their tendency to interact when in a convergent head-to-head orientation, it has been proposed that CTCF loops are formed via an extrusion mechanism involving cohesin (Alipour and Marko, 2012; Fudenberg et al., 2016; Nasmyth, 2001; Nichols and Corces, 2015; Sanborn et al., 2015).”
Cohesion and cohesin-dependent chromatin organization
Nishiyama, T. (2018) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2018.11.006 · Cited by 83
Rules of engagement for condensins and cohesins guide mitotic chromosome formation
Samejima, K., Gibcus, J. H., Abraham, S., Cisneros-Soberanis, F., Samejima, I., Beckett, A. J., Pucekova, N., Abad, M. A., Spanos, C., Medina‐Pritchard, B., et al. (2025) · Science · doi:10.1126/science.adq1709 · Cited by 78
Wang, X.-D., Hughes, A. C., Brandão, H. B., Walker, B. C., Lierz, C., Cochran, J. C., Oakley, M. G., Kruse, A., & Rudner, D. (2018) · Molecules and Cells · doi:10.1016/j.molcel.2018.07.006 · Cited by 71
“In this model, tethered rings (or a single ring embracing a small loop) load onto DNA and translocate away from this site processively enlarging a DNA loop (Alipour and Marko, 2012; Dekker and Mirny, 2016; Fudenberg et al., 2016; Goloborodko et al., 2016; Kimura et al., 1999; Nasmyth, 2001; Naumova et al., 2013; Nicho…”
BackgroundA cohesin traffic pattern genetically linked to gene regulation
Valton, A.-L., Venev, S. V., Mair, B., Khokhar, E. S., Tong, A. H. Y., Ušaj, M., Chan, K., Pai, A. A., Moffat, J., & Dekker, J. (2022) · Nature Structural & Molecular Biology · doi:10.1038/s41594-022-00890-9 · Cited by 83
Understanding the 3D genome: Emerging impacts on human disease
Krumm, A., & Duan, Z. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.07.004 · Cited by 76
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“and Smc ring states might allow continuous expansion of loops of chromosomal DNA formed at parS (Figure 7) (Alipour and Marko, 2012; Nasmyth, 2001).”
Chromatin jets define the properties of cohesin-driven in vivo loop extrusion.
Guo, Y., Al-Jibury, E., Garcia-Millan, R., Ntagiantas, K., King, J. W. D., Nash, A. J., Galjart, N., Lenhard, B., Rueckert, D., Fisher, A., et al. (2022) · Molecules and Cells · doi:10.1016/j.molcel.2022.09.003 · Cited by 69
How the Genome Folds: The Biophysics of Four-Dimensional Chromatin Organization
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Cohesin Can Remain Associated with Chromosomes during DNA Replication
Rhodes, J., Haarhuis, J. H. I., Grimm, J. B., Rowland, B. D., Lavis, L. D., & Nasmyth, K. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.092 · Cited by 67
“…these tripartite rings while topologically associating domains (TADs) have been postulated to arise through the extrusion of loops of chromatin fibres through these rings, a hypothesis known as loop extrusion (Alipour and Marko, 2012; Fudenberg et al., 2016; Nasmyth, 2001; Sanborn et al., 2015).”
BackgroundGu, B., Comerci, C. J., McCarthy, D. G., Saurabh, S., Moerner, W. E., & Wysocka, J. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.10.001 · Cited by 66
“from chromatin, collides with another cohesin complex, or encounters chromatin-bound CTCF barriers with a specific orientation (Alipour and Marko, 2012; Fudenberg et al., 2016; Sanborn et al., 2015).”
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 66
Orlandini, E., Marenduzzo, D., & Michieletto, D. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1815394116 · Cited by 65
The multiple facets of the SMC1A gene
Musio, A. (2020) · Gene · doi:10.1016/j.gene.2020.144612 · Cited by 62
“In silico simulations suggest a model according to which chromosomal domains are formed when loop extrusion factors, such as cohesin, translocate along DNA until they encounter a boundary element, as well as CTFC, that inhibits further translocation (Alipour and Marko, 2012; Fudenberg et al., 2016; Goloborodko et al.,…”
BackgroundSpatial Organization of Chromatin: Emergence of Chromatin Structure During Development
Ghosh, R. P., & Meyer, B. J. (2021) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-032321-035734 · Cited by 60
Tuned SMC Arms Drive Chromosomal Loading of Prokaryotic Condensin
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“Mole lysis, or it might represent processive diffusion along the substrate, driven by external motors or thermal motion (Alipour and Marko, 2012; Goloborodko et al., 2016; Nasmyth, 2001).”
BackgroundSMC complexes: Lifting the lid on loop extrusion
Higashi, T. L., & Uhlmann, F. (2022) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2021.12.003 · Cited by 58
Transient DNA Occupancy of the SMC Interarm Space in Prokaryotic Condensin
Nunez, R. J. V., Avila, L. B. R., & Gruber, S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.001 · Cited by 61
WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring
Kiefer, L., Chiosso, A., Langen, J., Buckley, A., Gaudin, S., Rajkumar, S. M., Servito, G., Cha, E. S., Vijay, A., Yeung, A. K. W., et al. (2023) · Science · doi:10.1126/science.adf8440 · Cited by 59
Engineering 3D genome organization
Wang, H., Han, M., & Qi, L. S. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-020-00325-5 · Cited by 62
Distinct Activities of Bacterial Condensins for Chromosome Management in Pseudomonas aeruginosa
Lioy, V. S., Junier, I., Lagage, V., Vallet-Gély, I., & Boccard, F. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108344 · Cited by 58
Multilayer chromosome organization through DNA bending, bridging and extrusion
Gruber, S. (2014) · Current Opinion in Microbiology · doi:10.1016/j.mib.2014.09.018 · Cited by 62
“On the other hand, a mechanism of DNA extrusion could create intra-chromosome loops of DNA and by doing so per se prevent the formation of any sister or arm interconnections (Figure 4e) [72].”
BackgroundUnderstanding Spatial Genome Organization: Methods and Insights
Ramani, V., Shendure, J., & Duan, Z. (2016) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.01.002 · Cited by 66
“This is in agreement with an extrusion model of loop formation [98,153].”
ResultChromosome disentanglement driven via optimal compaction of loop-extruded brush structures
Brahmachari, S., & Marko, J. F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906355116 · Cited by 54
“Processive extrusion of genomic loops by loop-extruding enzymes has been proposed to underlie lengthwise compaction (3, 8) and the formation of the long-observed cylindrical brush (loop array) structure of metaphase chromosomes (9–11).”
BackgroundSelf-citationCrossed wires: 3D genome misfolding in human disease
Norton, H. K., & Phillips-Cremins, J. E. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201611001 · Cited by 57
“An intriguing model based on loop extrusion has been proposed for the physical mechanism by which cohesin forms chromatin loops (Nasmyth, 2001; Alipour and Marko, 2012; Sanborn et al., 2015; Fudenberg et al., 2016).”
Nomidis, S. K., Carlon, E., Gruber, S., & Marko, J. (2022) · bioRxiv · doi:10.1093/nar/gkac268 · Cited by 48
“Many lines of evidence have long pointed to DNA or chromatin loop formation as a fundamental organizing principle of chromosome folding, and it has now become clear that the Structural Maintenance of Chromosomes (SMC) protein complexes are key drivers of DNA looping (1, 2, 3).”
BackgroundMethodInfluentialSelf-citationThe biology and polymer physics underlying large‐scale chromosome organization
Sazer, S., & Schießel, H. (2017) · Traffic · doi:10.1111/tra.12539 · Cited by 54
Escherichia coli Chromosomal Loci Segregate from Midcell with Universal Dynamics
Cass, J. A., Kuwada, N. J., Traxler, B. A., & Wiggins, P. A. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2016.04.046 · Cited by 55
Centromere Structure and Function
Bloom, K., & Costanzo, V. (2017) · Progress in molecular and subcellular biology · doi:10.1007/978-3-319-58592-5_21 · Cited by 51
“A second model that has been proposed is the activity of loop extrusion enzymes (Alipour and Marko 2012).”
Background3D genome organization: a role for phase separation and loop extrusion?
Stam, M. E., Tark‐Dame, M., & Fransz, P. F. (2019) · Current Opinion in Plant Biology · doi:10.1016/j.pbi.2019.03.008 · Cited by 54
Taking cohesin and condensin in context
Yuen, K. C. Y., & Gerton, J. L. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007118 · Cited by 54
Polymer physics of nuclear organization and function
Amitai, A., & Holcman, D. (2017) · Physics Reports · doi:10.1016/j.physrep.2017.02.002 · Cited by 53
Physical and data structure of 3D genome
Huang, K., Li, Y., Shim, A. R., Nap, R. J., Agrawal, V., Virk, R. K. A., Eshein, A., Almassalha, L. M., Backman, V., & Szleifer, I. G. (2020) · Science Advances · doi:10.1126/sciadv.aay4055 · Cited by 54
“Recent in vitro experiment (49) confirmed a condensin loop extrusion mechanism (50) on naked DNA, which is strictly one-sided and has been argued (51) to be far from sufficient for mitotic condensation.”
BackgroundBiophysics of protein–DNA interactions and chromosome organization
Marko, J. F. (2014) · Physica A Statistical Mechanics and its Applications · doi:10.1016/j.physa.2014.07.045 · Cited by 52
Self-citationMultistep assembly of DNA condensation clusters by SMC
Kim, H., & Loparo, J. J. (2016) · Nature Communications · doi:10.1038/ncomms10200 · Cited by 55
“Prior biochemical work concluded that BsSMC initially associates with DNA through its hinge domain and that binding is independent of ATP 17 , consistent with proposals that SMC binding and SMC-mediated DNA compaction are decoupled processes 38,58 .”
A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules
Gutiérrez-Escribano, P., Newton, M. D., Llauró, A., Huber, J., Tanasie, L., Davy, J., Aly, I., Aramayo, R. J., Montoya, A., Kramer, H., et al. (2019) · Science Advances · doi:10.1126/sciadv.aay6804 · Cited by 50
“HiC data show that removal of cohesin leads to loss of contacts at TAD boundaries (6, 8, 39), demonstrating that the complex is involved in the formation or maintenance of loops.”
The emergence of genome architecture and zygotic genome activation
Vallot, A., & Tachibana, K.-E. K. (2020) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.02.002 · Cited by 53
Extrusion without a motor: a new take on the loop extrusion model of genome organization
Brackley, C. A., Johnson, J., Michieletto, D., Morozov, A. N., Nicodemi, M., Cook, P. R., & Marenduzzo, D. (2018) · Nucleus · doi:10.1080/19491034.2017.1421825 · Cited by 52
“[6] E.”
BackgroundTheory and simulations of condensin mediated loop extrusion in DNA
Takaki, R., Dey, A., Shi, G., & Thirumalai, D. (2021) · Nature Communications · doi:10.1038/s41467-021-26167-1 · Cited by 50
From single genes to entire genomes: the search for a function of nuclear organization
Pueschel, R., Coraggio, F., & Meister, P. (2016) · Development · doi:10.1242/dev.129007 · Cited by 52
Genomic insights into chromatin reprogramming to totipotency in embryos
Ladstätter, S., & Tachibana, K.-E. K. (2018) · The Journal of Cell Biology · doi:10.1083/jcb.201807044 · Cited by 49
“Cohesin or its associated proteins are strong candidates for the loop extrusion factor, which has been proposed to progressively facilitate loop growth until encountering a boundary element (Nasmyth, 2001; Alipour and Marko, 2012; Sanborn et al., 2015; Fudenberg et al., 2016).”
BackgroundDeciphering multi-way interactions in the human genome
Dotson, G. A., Chen, C., Lindsly, S., Cicalo, A., Dilworth, S., Ryan, C. W., Jeyarajan, S., Meixner, W., Stansbury, C. M., Pickard, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32980-z · Cited by 48
“We 142 additionally investigated cohesin for its colocalization with CTCF and involvement in regulation of chromatin architecture, 143 such as chromatin loop extrusion [37, 38, 39, 40].”
BackgroundYY1-controlled regulatory connectivity and transcription are influenced by the cell cycle
Lam, J. C., Aboreden, N. G., Midla, S. C., Wang, S., Huang, A., Keller, C. A., Giardine, B. M., Henderson, K. A., Hardison, R. C., Zhang, H., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01871-y · Cited by 47
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A loop extrusion–independent mechanism contributes to condensin I–mediated chromosome shaping
Kinoshita, K., Tsubota, Y., Tane, S., Aizawa, Y., Sakata, R., Takeuchi, K., Shintomi, K., Nishiyama, T., & Hirano, T. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202109016 · Cited by 44
RAD21 is the core subunit of the cohesin complex involved in directing genome organization
Sun, Y., Xu, X., Zhao, W., Zhang, Y., Chen, K., Li, Y., Wang, X., Zhang, M., Xue, B., Yu, W., et al. (2023) · Genome biology · doi:10.1186/s13059-023-02982-1 · Cited by 46
“These results under different conditions were consistent with the CTCF/cohesin-anchored chromatin loop model [4, 8, 9, 11, 13, 21, 27, 31] (Fig.”
ResultShi, G., & Thirumalai, D. (2019) · Nature Communications · doi:10.1038/s41467-019-11897-0 · Cited by 48
The macro and micro of chromosome conformation capture
Goel, V. Y., & Hansen, A. S. (2020) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.395 · Cited by 48
“…of “DNA reeling” may explain loop folding dates back as far as 1990 (Riggs, Holliday, Monk, & Pugh, 1990), and modeling work conducted in the wake of the first observation of TADs theorized that a hypothetical DNA-loop-extruding enzyme could create and anchor loop domains (Alipour & Marko, 2012).”
Stefano, M. D., Paulsen, J., Jost, D., & Martı́-Renom, M. A. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.10.004 · Cited by 44
On the tree-like structure of rings in dense solutions
Michieletto, D. (2016) · Soft Matter · doi:10.1039/c6sm02168a · Cited by 46
Multi-scale architecture of archaeal chromosomes
Takemata, N., & Bell, S. D. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.12.001 · Cited by 47
Cell-Cycle Regulation of Dynamic Chromosome Association of the Condensin Complex
Thadani, R., Kamenz, J. L., Heeger, S., Muñoz, S., & Uhlmann, F. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.082 · Cited by 44
“An alternatively proposed condensation mechanism, that of loop extrusion or loop expansion, could also be aided by an increased mitotic condensin residence time (Alipour and Marko, 2012; Cheng et al., 2015; Fudenberg et al., 2016; Thadani et al., 2012).”
BackgroundChromatin Loop Extrusion and Chromatin Unknotting
Račko, D., Benedetti, F., Goundaroulis, D., & Stasiak, A. (2018) · Polymers · doi:10.3390/polym10101126 · Cited by 43
“Chromatin condensation mediated by the action of condensin helps to disentangle sister chromatids from each other but this is due to effective shortening of chromatids changing them from long, thin, and floppy filaments that easily entangle with each other to short, thick, and rigid rods that are unable to entangle wi…”
BackgroundChoppakatla, P., Dekker, B., Cutts, E., Vannini, A., Dekker, J., & Funabiki, H. (2021) · eLife · doi:10.7554/elife.68918 · Cited by 42
Theory of chromatin organization maintained by active loop extrusion
Chan, B., & Rubinstein, M. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2222078120 · Cited by 44
A tethered-inchworm model of SMC DNA translocation
Nichols, M. H., & Corces, V. G. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0135-4 · Cited by 41
Biggs, 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
“The currently heavily studied loop-extrusion model builds upon this classical bottlebrush model, describing how the bottlebrush is formed (Alipour and Marko, 2012; Goloborodko et al., 2016; Gibcus et al., 2018).”
BackgroundSelf-citationNucleosome positioning and chromatin organization
Parmar, J. J., & Padinhateeri, R. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.06.021 · Cited by 41
Wu, H., Zhang, J., Tan, L., & Xie, X. S. (2025) · Nature Genetics · doi:10.1038/s41588-025-02247-6 · Cited by 44
“We speculate that the concur-rence of nested CTCF loops is driven by the synergistic stabilization effect of spatially clustered CTCFs, which protects cohesin against WAPL-mediated release 44 .”
InfluentialCoupling 1D modifications and 3D nuclear organization: data, models and function
Jost, D., Vaillant, C., & Meister, P. (2016) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2016.12.001 · Cited by 42
“To account for that, a second class of models has recently emerged (Figure 2c), based on early speculations on mitotic condensation [58,59].”
BackgroundUlianov, S. V., Tachibana-Konwalski, K., & Razin, S. V. (2017) · BioEssays · doi:10.1002/bies.201700104 · Cited by 43
“array of consecutive loops in mitotic chromosomes [36, 47, 49, 53].”
BackgroundLeagues of their own: sexually dimorphic features of meiotic prophase I
Cahoon, C. K., & Libuda, D. E. (2019) · Chromosoma · doi:10.1007/s00412-019-00692-x · Cited by 39
Entropy gives rise to topologically associating domains
Vásquez, P. A., Hult, C., Adalsteinsson, D., Lawrimore, J., Forest, M. G., & Bloom, K. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw510 · Cited by 37
“It has been shown that chromatin loops influence the size and dynamic features of chromosome territories (21–28).”
BackgroundOligomerization and ATP stimulate condensin-mediated DNA compaction
Keenholtz, R. A., Dhanaraman, T., Palou, R., Yu, J., D'Amours, D., & Marko, J. (2017) · Scientific Reports · doi:10.1038/s41598-017-14701-5 · Cited by 39
Self-citationDNA sequence-dependent chromatin architecture and nuclear hubs formation
Jabbari, K., Chakraborty, M., & Wiehe, T. (2019) · Scientific Reports · doi:10.1038/s41598-019-51036-9 · Cited by 39
Interplay between Pds5 and Rec8 in regulating chromosome axis length and crossover frequency
Song, M., Zhai, B., Xiao, Y., Tan, T., Wang, Y., Yang, X., Tan, Y., Chu, T., Cao, Y., Song, Y., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe7920 · Cited by 38
“This suggests that cohesin is necessary for loop/axis formation, which is consistent with the loop extrusion model (22, 38).”
BackgroundResultEstablishment of dsDNA-dsDNA interactions by the condensin complex
Tang, M., Pobegalov, G. E., Tanizawa, H., Chen, Z. A., Rappsilber, J., Molodtsov, M. I., Noma, K.-I., & Uhlmann, F. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.09.019 · Cited by 33
Shaping of the 3D genome by the ATPase machine cohesin
Kim, Y., & Yu, H. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00526-2 · Cited by 34
Guiding functions of the C-terminal domain of topoisomerase IIα advance mitotic chromosome assembly
Shintomi, K., & Hirano, T. (2021) · Nature Communications · doi:10.1038/s41467-021-23205-w · Cited by 37
Single‐cell imaging of genome organization and dynamics
Xie, L., & Liu, Z. J. (2021) · Molecular Systems Biology · doi:10.15252/msb.20209653 · Cited by 35
Shaping centromeres to resist mitotic spindle forces
Lawrimore, J., & Bloom, K. (2022) · Journal of Cell Science · doi:10.1242/jcs.259532 · Cited by 37
Lassadi, I., Kamgoué, A., Goiffon, I., Gac, N. T. L., & Bystricky, K. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004306 · Cited by 42
“Chromatin fibers can be represented by a polymer random coil adopting a considerable, largely unappreciated number of states in response to DNAmetabolism [4–7].”
BackgroundThe spatial segregation of pericentric cohesin and condensin in the mitotic spindle
Stephens, A. D., Quammen, C., Chang, B., Haase, J., Taylor, R. M., & Bloom, K. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-06-0325 · Cited by 36
“(Melby et al., 1998; Strick et al., 2004; Alipour and Marko, 2012).”
BackgroundInfluentialWang, C., Nanni, L., Novakovic, B., Megchelenbrink, W., Kuznetsova, T., Stunnenberg, H. G., Ceri, S., & Logie, C. (2019) · Scientific Reports · doi:10.1038/s41598-019-39395-9 · Cited by 38
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
DNA double-strand break end synapsis by DNA loop extrusion
Yang, J. H., Brandão, H. B., & Hansen, A. S. (2023) · Nature Communications · doi:10.1038/s41467-023-37583-w · Cited by 36
Caenorhabditis elegans Dosage Compensation: Insights into Condensin-Mediated Gene Regulation
Albritton, S. E., & Ercan, S. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.09.010 · Cited by 33
“A series of tandem condensin-mediated loops may be made progressively larger by a process termed “loop extrusion,” wherein condensin actively pushes DNA through its ring [19, 20].”
Cohesin biology meets the loop extrusion model
Barrington, C., Finn, R., & Hadjur, S. (2017) · Chromosome Research · doi:10.1007/s10577-017-9550-3 · Cited by 38
“Recently, a mechanistic model based on in silico simulations has been put forward to explain chromosomal domain formation (Fudenberg et al. 2016; Goloborodko et al. 2016; Alipour and Marko 2012).”
BackgroundInfluentialComputational methods for analyzing and modeling genome structure and organization
Lin, D., Bonora, G., Yardımcı, G. G., & Noble, W. S. (2018) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1435 · Cited by 37
“This process was described in the so-called “ loop-extrusion model ” (Figure 2b) (Fudenberg et al., 2016; Sanborn et al., 2015), with similar models having previously been hypothesized to play a role during mitosis (Alipour & Marko, 2012; Riggs, 1990).”
MethodHow DNA loop extrusion mediated by cohesin enables V(D)J recombination
Peters, J. (2021) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2020.11.007 · Cited by 37
Limits of Chromosome Compaction by Loop-Extruding Motors
Banigan, E. J., & Mirny, L. A. (2019) · Physical Review X · doi:10.1103/physrevx.9.031007 · Cited by 35
Chan, B., & Rubinstein, M. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2401494121 · Cited by 34
“We consider active loop extrusion, in which cohesin uses adenosine triphospate (ATP) to move in biased directions toward domain boundaries (7–9, 11, 12).”
3D genome folding in epigenetic regulation and cellular memory
Paldi, F., & Cavalli, G. (2025) · Trends in Cell Biology · doi:10.1016/j.tcb.2025.03.001 · Cited by 34
“The visionary idea of loop extrusion dates back to 2001 [156], with initial evidence coming only a decade later from in silico models that indicated that loop extrusion can explain key aspects of chromatin loop and domain formation [157–159].”
A Topology-Centric View on Mitotic Chromosome Architecture
Piskadlo, E., & Oliveira, R. A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122751 · Cited by 30
Insights about genome function from spatial organization of the genome
Roy, S. S., Mukherjee, A. K., & Chowdhury, S. (2018) · Human Genomics · doi:10.1186/s40246-018-0140-z · Cited by 32
“In this model, a pair of factors (Cohesin), possibly with motor function, can dynamically bind to DNA and move along the DNA in opposite directions extruding the chromatin to form loops in between until they dissociate or stall at a boundary element (CTCF motif) [53 – 55].”
BackgroundGalupa, R., & Heard, É. (2017) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2017.82.035030 · Cited by 30
Metadata
- Authors
- Alipour, E., & Marko, J. F.
- Affiliations
- UConn Health (US)
- Northwestern University (US)
- Corresponding author
- Alipour, E.
- Marko, J. F.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-15
- Volume
- 40
- Issue
- 22
- Pages
- 11202-11212
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3526278
- OpenAlex
- W2100148696
- Cited by
- 540
- References
- 48
- Citations by year
- 2026: 26 · 2025: 45 · 2024: 44 · 2023: 46 · 2022: 38 · 2021: 55 · 2020: 71 · 2019: 61 · 2018: 54 · 2017: 52 · 2016: 27 · 2015: 10 · 2014: 7 · 2013: 3
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Science Foundation (1206868, 1022117, 0715099)
- National Institutes of Health (MCB-1022117, DMR-1206868)
- National Cancer Institute (U54CA143869)
- Division of Materials Research (DMR-1206868)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- DNA loop extrusion, self-organization, molecular machines, DNA translocation, processivity, loop size distribution, chromosome compaction, type I restriction enzymes, boundary elements
- MeSH terms
- Chromosomes, Computer Simulation, DNA, Enzymes, Models, Genetic, Nucleic Acid Conformation
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