Skip to main content
SpringerLink
Log in

Domain Model of Eukaryotic Genome Organization: From DNA Loops Fixed on the Nuclear Matrix to TADs

  • REVIEW
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

The article reviews the development of ideas on the domain organization of eukaryotic genome, with special attention on the studies of DNA loops anchored to the nuclear matrix and their role in the emergence of the modern model of eukaryotic genome spatial organization. Critical analysis of results demonstrating that topologically associated chromatin domains are structural-functional blocks of the genome supports the notion that these blocks are fundamentally different from domains whose existence was proposed by the domain hypothesis of eukaryotic genome organization formulated in the 1980s. Based on the discussed evidence, it is concluded that the model postulating that eukaryotic genome is built from uniformly organized structural-functional blocks has proven to be untenable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

Abbreviations

DNase:

deoxyribonuclease I

kb:

thousand base pairs

S/MAR:

DNA sequence that preferentially binds to the nuclear matrix

TAD:

topological associated chromatin domain

References

  1. Olins, A. L., and Olins, D. E. (1974) Spheroid chromatin units ([nu] bodies), Science, 183, 330-332, https://doi.org/10.1126/science.183.4122.330.

    Article  CAS  PubMed  Google Scholar 

  2. Axel, R. (1975) Cleavage of DNA in nuclei and chromatin with staphylococcal nuclease, Biochemistry, 14, 2921-2925, https://doi.org/10.1021/bi00684a020.

    Article  CAS  PubMed  Google Scholar 

  3. Finch, J. T., and Klug, A. (1976) Solenoidal model for superstructure in chromatin, Proc. Natl. Acad. Sci. USA, 73, 1897-1901, https://doi.org/10.1073/pnas.73.6.1897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rydberg, B., Holley, W. R., Mian, I. S., and Chatterjee, A. (1998) Chromatin conformation in living cells: support for a zig-zag model of the 30 nm chromatin fiber, J. Mol. Biol., 284, 71-84, https://doi.org/10.1006/jmbi.1998.2150.

    Article  CAS  PubMed  Google Scholar 

  5. Cook, P. R., Brazell, I. A., and Jost, E. (1976) Characterization of nuclear structures containing superhelical DNA, J. Cell. Sci., 22, 303-324, https://doi.org/10.1242/jcs.22.2.303.

    Article  CAS  PubMed  Google Scholar 

  6. Cook, P. R., and Brazell, I. A. (1975) Supercoils in human DNA, J. Cell Sci., 19, 261-279, https://doi.org/10.1242/jcs.19.2.261.

    Article  CAS  PubMed  Google Scholar 

  7. Berezney, R., and Coffey, D. S. (1975) Nuclear protein matrix: association with newly synthesized DNA, Science, 189, 291-293, https://doi.org/10.1126/science.1145202.

    Article  CAS  PubMed  Google Scholar 

  8. Jackson, D. A., and Cook, P. R. (1985) Transcription occurs at a nucleoskeleton, EMBO J., 4, 919-925, https://doi.org/10.1002/j.1460-2075.1985.tb03719.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Benyajati, C., and Worcel, A. (1976) Isolation, characterization, and structure of the folded interphase genome of Drosophila melanogaster, Cell, 9, 393-407, https://doi.org/10.1016/0092-8674(76)90084-2.

    Article  CAS  PubMed  Google Scholar 

  10. Igo-Kemennes, T., and Zachau, H. G. (1977) Domains in chromatin structure, Cold Spring Harbor Symp. Quant. Biol., 42, 109-118.

    Article  Google Scholar 

  11. Razin, S. V., Mantieva, V. L., and Georgiev, G. P. (1979) The similarity of DNA sequences remaining bound to scaffold upon nuclease treatment of interphase nuclei and metaphase chromosomes, Nucleic Acids Res., 7, 1713-1735, https://doi.org/10.1093/nar/7.6.1713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Adolph, K. W., Chang, S. M., and Laemmli, U. K. (1977) Role of nonhistone proteins in metaphase chromosomes structure, Cell, 12, 805-816, https://doi.org/10.1016/0092-8674(77)90279-3.

    Article  CAS  PubMed  Google Scholar 

  13. Hancock, R., and Hughes, M. E. (1982) Organization of DNA in the eukaryotic nucleus, Biol. Cell, 44, 201-212.

    CAS  Google Scholar 

  14. Razin, S. V., Gromova, I. I., and Iarovaia, O. V. (1995) Specificity and functional significance of DNA interaction with the nuclear matrix: new approaches to clarify the old questions, Int. Rev. Cytol., 162B, 405-448, https://doi.org/10.1016/s0074-7696(08)62623-6.

    Article  CAS  PubMed  Google Scholar 

  15. Mullenders, L. H., van Zeeland, A. A., and Natarajan, A. T. (1983) Comparison of DNA loop size and super-coiled domain size in human cells, Mutat. Res., 112, 245-252, https://doi.org/10.1016/0167-8817(83)90010-x.

    Article  CAS  PubMed  Google Scholar 

  16. Pienta, K. J., and Coffey, D. S. (1984) A structural analysis of the role of the nuclear matrix and DNA loops in the organization of the nucleus and chromosome, J. Cell Sci. Suppl., 1, 123-135, https://doi.org/10.1242/jcs.1984.supplement_1.9.

    Article  CAS  PubMed  Google Scholar 

  17. Borland, L., Harauz, G., Bahr, G., and van Heel, M. (1988) Packing of the 30 nm chromatin fiber in the human metaphase chromosome, Chromosoma, 97, 159-163, https://doi.org/10.1007/BF00327373.

    Article  CAS  PubMed  Google Scholar 

  18. Getzenberg, R. H., Pienta, K. J., Ward, W. S., and Coffey, D. S. (1991) Nuclear structure and the three-dimensional organization of DNA, J. Cell Biochem., 47, 289-299, https://doi.org/10.1002/jcb.240470402.

    Article  CAS  PubMed  Google Scholar 

  19. Weintraub, H., and Groudine, M. (1976) Chromosomal subunits in active genes have an altered conformation, Science, 73, 848-856, https://doi.org/10.1126/science.948749.

    Article  Google Scholar 

  20. Stalder, J., Larsen, A., Engel, J. D., Dolan, M., Groudine, M., et al. (1980) Tissue-specific DNA cleavages in the globin chromatin domain introduced by DNAase I, Cell, 20, 451-460, https://doi.org/10.1016/0092-8674(80)90631-5.

    Article  CAS  PubMed  Google Scholar 

  21. Lawson, G. M., Knoll, B. J., March, C. J., Woo, S. L. C., Tsai, M.-J., et al. (1982) Definition of 5′ and 3′ structural boundaries of the chromatin domain containing the ovalbumin multigene family, J. Biol. Chem., 257, 1501-1507, https://doi.org/10.1016/S0021-9258(19)68221-9.

    Article  CAS  PubMed  Google Scholar 

  22. Lawson, G. M., Tsai, M. J., and O’Malley, B. W. (1980) Deoxyribonuclease I sensitivity of the nontranscribed sequences flanking the 5′ and 3′ ends of the ovomucoid gene and the ovalbumin and its related X and Y genes in hen oviduct nuclei, Biochemistry, 19, 4403-4441, https://doi.org/10.1021/bi00560a004.

    Article  CAS  PubMed  Google Scholar 

  23. Bodnar, J. W. (1988) A domain model for eukaryotic DNA organization: a molecular basis for cell differentiation and chromosome evolution, J. Theor. Biol., 132, 479-507, https://doi.org/10.1016/s0022-5193(88)80086-9.

    Article  CAS  PubMed  Google Scholar 

  24. Goldman, M. A. (1988) The chromatin domain as a unit of gene regulation, Bioessays, 9, 50-55, https://doi.org/10.1002/bies.950090204.

    Article  CAS  PubMed  Google Scholar 

  25. Razin, S. V., Iarovaia, O. V., Sjakste, N., Sjakste, T., Bagdoniene, L., et al. (2007) Chromatin domains and regulation of transcription, J. Mol. Biol., 369, 597-607, https://doi.org/10.1016/j.jmb.2007.04.003.

    Article  CAS  PubMed  Google Scholar 

  26. Grosveld, F., van Assandelt, G. B., Greaves, D. R., and Kollias, B. (1987) Position-independent, high-level expression of the human b-globin gene in transgenic mice, Cell, 51, 975-985, https://doi.org/10.1016/0092-8674(87)90584-8.

    Article  CAS  PubMed  Google Scholar 

  27. Forrester, W. C., Epner, E., Driscoll, M. C., Enver, T., Brice, M., et al. (1990) A deletion of the human b-globin locus activation region causes a major alteration in chromatin structure and replication across the entire b-globin locus, Genes Dev., 4, 1637-1649, https://doi.org/10.1101/gad.4.10.1637.

    Article  CAS  PubMed  Google Scholar 

  28. Razin, S. V. (1996) Functional architecture of chromosomal DNA domains, Crit. Rev. Eukar. Gene Expr., 6, 247-269, https://doi.org/10.1615/critreveukargeneexpr.v6.i2-3.70.

    Article  CAS  Google Scholar 

  29. Cook, P. R., and Brazell, I. A. (1980) Mapping sequences in loops of nuclear DNA by their progressive detachment from the nuclear cage, Nucleic Acids Res., 8, 2895-2907, https://doi.org/10.1093/nar/8.13.2895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Robinson, S. I., Nelkin, B. D., and Volgelstein, B. (1982) The ovalbumin gene is associated with the nuclear matrix of chicken oviduct cells, Cell, 28, 99-106, https://doi.org/10.1016/0092-8674(82)90379-8.

    Article  CAS  PubMed  Google Scholar 

  31. Robinson, S. I., Small, D., Idzerda, R., McKnight, G. S., and Vogelstein, B. (1983) The association of active genes with the nuclear matrix of the chicken oviduct, Nucleic Acids Res., 15, 5113-5130, https://doi.org/10.1093/nar/11.15.5113.

    Article  Google Scholar 

  32. Small, D., Nelkin, B., and Vogelstein, B. (1985) The association of transcribed genes with the nuclear matrix of Drosophila cells during heat shock, Nucleic Acids Res., 13, 2413-2431, https://doi.org/10.1093/nar/13.7.2413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cook, P. R. (1989) The nucleoskeleton and the topology of transcription, Eur. J. Biochem., 185, 487-501, https://doi.org/10.1111/j.1432-1033.1989.tb15141.x.

    Article  CAS  PubMed  Google Scholar 

  34. Cook, P. R. (1991) The nucleoskeleton and the topology of replication, Cell, 66, 627-635, https://doi.org/10.1016/0092-8674(91)90109-c.

    Article  CAS  PubMed  Google Scholar 

  35. Cook, P. R. (1999) The organization of replication and transcription, Science, 284, 1790-1795, https://doi.org/10.1126/science.284.5421.1790.

    Article  CAS  PubMed  Google Scholar 

  36. Iborra, F. J., Pombo, A., Jackson, D. A., and Cook, P. R. (1996) Active RNA polymerases are localized within discrete transcription “factories” in human nuclei, J. Cell Sci., 109 (Pt 6), 1427-1436, https://doi.org/10.1242/jcs.109.6.1427.

    Article  Google Scholar 

  37. Hozak, P., Hassan, A. B., Jackson, D. A., and Cook, P. R. (1993) Visualization of replication factories attached to nucleoskeleton, Cell, 73, 361-373, https://doi.org/10.1016/0092-8674(93)90235-i.

    Article  CAS  PubMed  Google Scholar 

  38. Cook, P. R., and Marenduzzo, D. (2018) Transcription-driven genome organization: a model for chromosome structure and the regulation of gene expression tested through simulations, Nucleic Acids Res., 46, 9895-9906, https://doi.org/10.1093/nar/gky763.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bertero, A. (2021) RNA biogenesis instructs functional inter-chromosomal genome architecture, Front. Genet., 12, 645863, https://doi.org/10.3389/fgene.2021.645863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Razin, S. V. (1987) DNA interaction with the nuclear matrix and spatial organization of replication and transcription, BioEssays, 6, 19-23, https://doi.org/10.1002/bies.950060106.

    Article  CAS  PubMed  Google Scholar 

  41. Mirkovitch, J., Mirault, M.-E., and Laemmli, U. K. (1984) Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold, Cell, 39, 223-232, https://doi.org/10.1016/0092-8674(84)90208-3.

    Article  CAS  PubMed  Google Scholar 

  42. Cockerill, P. N., and Garrard, W. T. (1986) Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the nenhancer in a region containing topoisomerase II sites, Cell, 44, 273-282, https://doi.org/10.1016/0092-8674(86)90761-0.

    Article  CAS  PubMed  Google Scholar 

  43. Bode, J., Schlake, T., Rios-Ramirez, M., Mielke, C., Stengert, M., et al. (1995) Scaffold/matrix-attached regions: Structural properties creating transcriptionally active loci, Int. Rev. Cytol., 162A, 389-454, https://doi.org/10.1016/s0074-7696(08)61235-8.

    Article  CAS  PubMed  Google Scholar 

  44. Mirkovitch, J., Spierer, P., and Laemmli, U. K. (1986) Genes and loops in 320,000 base-pairs of the Drosophila melanogaster chromosome, J. Mol. Biol., 190, 255-258, https://doi.org/10.1016/0022-2836(86)90296-2.

    Article  CAS  PubMed  Google Scholar 

  45. Gasser, S. M., and Laemmli, U. K. (1986) Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster, Cell, 46, 521-530, https://doi.org/10.1016/0092-8674(86)90877-9.

    Article  CAS  PubMed  Google Scholar 

  46. Schwartz, Y. B., Ioudinkova, E. S., Demakov, S. A., Razin, S. V., and Zhimulev, I. F. (1999) Interbands of Drosophila melanogaster polytene chromosomes contain matrix association regions, J. Cell Biochem., 72, 368-372, https://doi.org/10.1002/(SICI)1097-4644(19990301)72:3<368::AID-JCB6>3.0.CO;2-C.

    Article  CAS  PubMed  Google Scholar 

  47. Levy-Wilson, B., and Fortier, C. (1989) The limits of the DNase I-sensitive domain of the human apolipoprotein B gene coincide with the locations of chromosomal anchorage loops and define the 5′ and 3′ boundarires of the gene, J. Biol. Chem., 264, 21196-22204, https://doi.org/10.1016/S0021-9258(19)30066-3.

    Article  CAS  PubMed  Google Scholar 

  48. Pathak, R. U., Srinivasan, A., and Mishra, R. K. (2014) Genome-wide mapping of matrix attachment regions in Drosophila melanogaster, BMC Genomics, 15, 1022, https://doi.org/10.1186/1471-2164-15-1022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Liebich, I., Bode, J., Reuter, I., and Wingender, E. (2002) Evaluation of sequence motifs found in scaffold/matrix-attached regions (S/MARs), Nucleic Acids Res., 30, 3433-3442, https://doi.org/10.1093/nar/gkf446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Boulikas, T. (1992) Homeotic protein binding sites, origins of replication, and nuclear matrix anchorage sites share the ATTA and ATTTA motifs, J. Cell Biochem., 50, 111-123, https://doi.org/10.1002/jcb.240500202.

    Article  CAS  PubMed  Google Scholar 

  51. Gasser, S. M., and Laemmli, U. K. (1986) The organization of chromatin loops: characterization of a scaffold attachment site, EMBO J., 5, 511-518, https://doi.org/10.1002/j.1460-2075.1986.tb04240.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Adachi, Y., Käs, E., and Laemmli, U. K. (1989) Preferential, cooperative binding of DNA topoisomerase II to scaffold-associated regions, EMBO J., 8, 3997-4006, https://doi.org/10.1002/j.1460-2075.1989.tb08582.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bode, J., Winkelmann, S., Gotze, S., Spiker, S., Tsutsui, K., et al. (2006) Correlations between scaffold/matrix attachment region (S/MAR) binding activity and DNA duplex destabilization energy, J. Mol. Biol., 358, 597-613, https://doi.org/10.1016/j.jmb.2005.11.073.

    Article  CAS  PubMed  Google Scholar 

  54. Attal, J., Cajero-Juarez, M., Petitclerc, D., Theron, M. C., Stinnakre, M. G., et al. (1995) The effect of matrix attached regions (MAR) and specialized chromatin structure (SCS) on the expression of gene constructs in cultured cells and in transgenic mice, Mol. Biol. Rep., 22, 37-46, https://doi.org/10.1007/BF00996303.

    Article  CAS  PubMed  Google Scholar 

  55. McKnight, R. A., Shamay, A., Sankaran, L., Wall, R. J., and Hennighausen, L. (1992) Matrix-attachment regions can impart position-independent regulation of a tissue-specific gene in transgenic mice, Proc. Natl. Acad. Sci. USA, 89, 6943-6947, https://doi.org/10.1073/pnas.89.15.6943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. De Bolle, M. F., Butaye, K. M., Goderis, I. J., Wouters, P. F., Jacobs, A., et al. (2007) The influence of matrix attachment regions on transgene expression in Arabidopsis thaliana wild type and gene silencing mutants, Plant Mol. Biol., 63, 533-543, https://doi.org/10.1007/s11103-006-9107-x.

    Article  CAS  PubMed  Google Scholar 

  57. Kellum, R., and Schedl, P. (1992) A group of scs elements function as boundaries in enhancer-blocking assay, Mol. Cell. Biol., 12, 2424-2431, https://doi.org/10.1128/mcb.12.5.2424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhao, C. P., Guo, X., Chen, S. J., Li, C. Z., Yang, Y., et al. (2017) Matrix attachment region combinations increase transgene expression in transfected Chinese hamster ovary cells, Sci. Rep., 7, 42805, https://doi.org/10.1038/srep42805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Ji, L., Xu, R., Lu, L., Zhang, J., Yang, G., et al. (2013) TM6, a novel nuclear matrix attachment region, enhances its flanking gene expression through influencing their chromatin structure, Mol. Cells, 36, 127-137, https://doi.org/10.1007/s10059-013-0092-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Fukuda, Y., and Nishikawa, S. (2003) Matrix attachment regions enhance transcription of a downstream transgene and the accessibility of its promoter region to micrococcal nuclease, Plant Mol. Biol., 51, 665-675, https://doi.org/10.1023/a:1022509909838.

    Article  CAS  PubMed  Google Scholar 

  61. Izaurralde, E., Mirkovich, J., and Laemmli, U. K. (1988) Interaction of DNA with nuclear scaffolds in vitro, J. Mol. Biol., 200, 111-125, https://doi.org/10.1016/0022-2836(88)90337-3.

    Article  CAS  PubMed  Google Scholar 

  62. Wang, T. Y., Han, Z. M., Chai, Y. R., and Zhang, J. H. (2010) A mini review of MAR-binding proteins, Mol. Biol. Rep., 37, 3553-3560, https://doi.org/10.1007/s11033-010-0003-8.

    Article  CAS  PubMed  Google Scholar 

  63. Naik, R., and Galande, S. (2019) SATB family chromatin organizers as master regulators of tumor progression, Oncogene, 38, 1989-2004, https://doi.org/10.1038/s41388-018-0541-4.

    Article  CAS  PubMed  Google Scholar 

  64. Marenda, M., Lazarova, E., and Gilbert, N. (2022) The role of SAF-A/hnRNP U in regulating chromatin structure, Curr. Opin. Gen. Dev., 72, 38-44, https://doi.org/10.1016/j.gde.2021.10.008.

    Article  CAS  Google Scholar 

  65. Chattopadhyay, S., and Pavithra, L. (2007) MARs and MARBPs: key modulators of gene regulation and disease manifestation, Subcell Biochem., 41, 213-230.

    PubMed  Google Scholar 

  66. Schwartz, D. C., and Cantor, C. R. (1984) Separation of yeast chromosome-sized DNAs by pulsed field gradient gel electrophoresis, Cell, 37, 67-75, https://doi.org/10.1016/0092-8674(84)90301-5.

    Article  CAS  PubMed  Google Scholar 

  67. Razin, S. V., Hancock, R., Iarovaia, O., Westergaard, O., Gromova, I., et al. (1993) Structural-functional organization of chromosomal DNA domains, Cold Spring Harbor Symp.Quant. Biol., 58, 25-35, https://doi.org/10.1101/sqb.1993.058.01.006.

    Article  CAS  PubMed  Google Scholar 

  68. Razin, S. V., Petrov, P., and Hancock, R. (1991) Precise localization of the a-globin gene cluster within one of the 20- to 300-Kilobase DNA fragment released by cleavage of chicken chromosomal DNA at topoisomerase II site in vivo: evidence that the fragment are DNA loops or domains, Proc. Natl. Acad. Sci. USA, 88, 8515-8519, https://doi.org/10.1073/pnas.88.19.8515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Liu, L. F. (1983) DNA topoisomerases – enzymes that catalyse the breaking and rejoining of DNA, CRC Crit. Rev. Biochem., 15, 1-24, https://doi.org/10.3109/10409238309102799.

    Article  CAS  PubMed  Google Scholar 

  70. Liu, L. F. (1989) DNA topoisomerase poisons as antitumor drugs, Annu. Rev. Biochem., 58, 351-375, https://doi.org/10.1146/annurev.bi.58.070189.002031.

    Article  CAS  PubMed  Google Scholar 

  71. Berrios, M., Osheroff, N., and Fischer, P. A. (1985) In situ localization of DNA topoisomerase II, a major polypeptide component of the Drosophila nuclear matrix fraction, Proc. Natl. Acad. Sci. USA, 82, 4142-4146, https://doi.org/10.1073/pnas.82.12.4142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Gasser, S. M., Laroche, T., Falquet, J., Boy de la Tour, E., and Laemmli, U. K. (1986) Metaphase chromosome structure. Involvement of topoisomerase II, J. Mol. Biol., 188, 613-629, https://doi.org/10.1016/s0022-2836(86)80010-9.

    Article  CAS  PubMed  Google Scholar 

  73. Nedospasov, S. A., and Georgiev, G. P. (1980) Non-random cleavage of SV40 DNA in the compact minichromosome and free in solution by micrococcal nuclease, Biochem. Biophys. Res. Commun., 92, 532-539, https://doi.org/10.1016/0006-291x(80)90366-6.

    Article  CAS  PubMed  Google Scholar 

  74. Gromova, I. I., Thomsen, B., and Razin, S. V. (1995) Different topoisomerase II antitumor drugs direct similar specific long-range fragmentation of an amplified c-MYC gene locus in living cells and in high-salt-extracted nuclei, Proc. Natl. Acad. Sci. USA, 92, 102-106, https://doi.org/10.1073/pnas.92.1.102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Iarovaia, O., Hancock, R., Lagarkova, M., Miassod, R., and Razin, S. V. (1996) Mapping of genomic DNA loop organization in a 500-kilobase region of the Drosophila X chromosome by the topoisomerase II-mediated DNA loop excision protocol, Mol. Cell Biol., 16, 302-308, https://doi.org/10.1128/mcb.16.1.302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Iarovaia, O. V., Bystritskiy, A., Ravcheev, D., Hancock, R., and Razin, S. V. (2004) Visualization of individual DNA loops and a map of loop-domains in the human dystrophin gene, Nucleic Acids Res., 32, 2079-2086, https://doi.org/10.1093/nar/gkh532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lagarkova, M. A., Iarovaia, O. V., and Razin, S. V. (1995) The large-scale fragmentation of mammalian DNA in the course of apoptosis proceeds via excision of chromosomal DNA loops and their oligomers, J. Biol. Chem., 270, 20239-20241, https://doi.org/10.1074/jbc.270.35.20239.

    Article  CAS  PubMed  Google Scholar 

  78. Solovyan, V. T., Bezvenyuk, Z. A., Salminen, A., Austin, C. A., and Courtney, M. J. (2002) The role of topoisomerase II in the excision of DNA loop domains during apoptosis, J. Biol. Chem., 277, 21458-21467, https://doi.org/10.1074/jbc.M110621200.

    Article  CAS  PubMed  Google Scholar 

  79. Bezvenyuk, Z., Salminen, A., and Solovyan, V. (2000) Excision of DNA loop domains as a common step in caspase-dependent and -independent types of neuronal cell death, Brain Res. Mol. Brain Res., 81, 191-196, https://doi.org/10.1016/s0169-328x(00)00174-1.

    Article  CAS  PubMed  Google Scholar 

  80. Rho, J. H., Kang, D. Y., Park, K. J., Choi, H. J., Lee, H. S., et al. (2005) Doxorubicin induces apoptosis with profile of large-scale DNA fragmentation and without DNA ladder in anaplastic thyroid carcinoma cells via histone hyperacetylation, Int. J. Oncol., 27, 465-471, https://doi.org/10.3892/ijo.27.2.465.

    Article  CAS  PubMed  Google Scholar 

  81. Li, T. K., Chen, A. Y., Yu, C., Mao, Y., Wang, H., et al. (1999) Activation of topoisomerase II-mediated excision of chromosomal DNA loops during oxidative stress, Genes Dev., 13, 1553-1560, https://doi.org/10.1101/gad.13.12.1553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Gromova, I. I., Nielsen, O. F., and Razin, S. V. (1995) Long-range fragmentation of the eukaryotic genome by exogenous and endogenous nucleases proceeds in a specific fashion via preferential DNA cleavage at matrix attachment sites, J. Biol. Chem., 270, 18685-18690, https://doi.org/10.1074/jbc.270.31.18685.

    Article  CAS  PubMed  Google Scholar 

  83. Lagarkova, M. A., Iarovaia, O. V., and Razin, S. V. (1995) Excision of chromosomal DNA loops by pretreatment of permeabilised cells with Bal 31 nuclease, Mol. Gen. Genet., 249, 253-256, https://doi.org/10.1007/BF00290373.

    Article  CAS  PubMed  Google Scholar 

  84. Sotolongo, B., Huang, T. T., Isenberger, E., and Ward, W. S. (2005) An endogenous nuclease in hamster, mouse, and human spermatozoa cleaves DNA into loop-sized fragments, J. Androl., 26, 272-280, https://doi.org/10.1002/j.1939-4640.2005.tb01095.x.

    Article  CAS  PubMed  Google Scholar 

  85. Hancock, R. (2000) A new look at the nuclear matrix, Chromosoma, 109, 219-225, https://doi.org/10.1007/s004120000077.

    Article  CAS  PubMed  Google Scholar 

  86. Pederson, T. (2000) Half a century of “the nuclear matrix”, Mol. Biol. Cell, 11, 799-805, https://doi.org/10.1091/mbc.11.3.799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Razin, S. V., Iarovaia, O. V., and Vassetzky, Y. S. (2014) A requiem to the nuclear matrix: from a controversial concept to 3D organization of the nucleus, Chromosoma, 123, 217-224, https://doi.org/10.1007/s00412-014-0459-8.

    Article  CAS  PubMed  Google Scholar 

  88. Svetlova, E. Y., Razin, S. V., and Debatisse, M. (2001) Mammalian recombination hot spot and DNA loop anchorage region: a model for the study of common fragile sites, J. Cell. Biochem., S36, 170-178, https://doi.org/10.1002/jcb.1081.

    Article  Google Scholar 

  89. Stanulla, M., Wang, J., Chervinsky, D. S., Thandla, S., and Aplan, P. D. (1997) DNA cleavage within the MLL breakpoint cluster region is a specific event which occurs as part of higher-order chromatin fragmentation during the initial stages of apoptosis, Mol. Cell. Biol., 17, 4070-4079, https://doi.org/10.1128/MCB.17.7.4070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Aplan, P. D., Chervinsky, D. S., Stanulla, M., and Burhans, W. C. (1996) Site-specific DNA cleavage within the MLL breakpoint cluster region induced by topoisomerase II inhibitors, Blood, 87, 2649-2658.

    Article  CAS  Google Scholar 

  91. Felix, C. A. (1998) Secondary leukemias induced by topoisomerase-targeted drugs, Biochim. Biophys. Acta, 1400, 233-255, https://doi.org/10.1016/s0167-4781(98)00139-0.

    Article  CAS  PubMed  Google Scholar 

  92. Razin, S. V. (1999) Chromosomal DNA loops may constitute basic units of the genome organization and evolution, Crit. Rev. Eukar. Gene Exp., 9, 279-283, https://doi.org/10.1615/critreveukargeneexpr.v9.i3-4.120.

    Article  CAS  Google Scholar 

  93. Kantidze, O. L., and Razin, S. V. (2009) Chromatin loops, illegitimate recombination, and genome evolution, Bioessays, 31, 278-286, https://doi.org/10.1002/bies.200800165.

    Article  CAS  PubMed  Google Scholar 

  94. Lawrence, J. B., Singer, R. H., and McNeil, J. A. (1990) Interphase and metaphase resolution of different distances within the human dystrophin gene, Science, 249, 928-932, https://doi.org/10.1126/science.2203143.

    Article  CAS  PubMed  Google Scholar 

  95. Hu, Y., Kireev, I., Plutz, M., Ashourian, N., and Belmont, A. S. (2009) Large-scale chromatin structure of inducible genes: transcription on a condensed, linear template, J. Cell Biol., 185, 87-100, https://doi.org/10.1083/jcb.200809196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Fussner, E., Strauss, M., Djuric, U., Li, R., Ahmed, K., et al. (2012) Open and closed domains in the mouse genome are configured as 10-nm chromatin fibres, EMBO Rep., 13, 992-996, https://doi.org/10.1038/embor.2012.139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Nishino, Y., Eltsov, M., Joti, Y., Ito, K., Takata, H., et al. (2012) Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure, EMBO J., 31, 1644-1653, https://doi.org/10.1038/emboj.2012.35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Eltsov, M., Maclellan, K. M., Maeshima, K., Frangakis, A. S., and Dubochet, J. (2008) Analysis of cryo-electron microscopy images does not support the existence of 30-nm chromatin fibers in mitotic chromosomes in situ, Proc. Natl. Acad. Sci. USA, 105, 19732-19737, https://doi.org/10.1073/pnas.0810057105.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Maeshima, K., Imai, R., Hikima, T., and Joti, Y. (2014) Chromatin structure revealed by X-ray scattering analysis and computational modeling, Methods, 70, 154-161, https://doi.org/10.1016/j.ymeth.2014.08.008.

    Article  CAS  PubMed  Google Scholar 

  100. Joti, Y., Hikima, T., Nishino, Y., Kamada, F., Hihara, S., et al. (2012) Chromosomes without a 30-nm chromatin fiber, Nucleus, 3, 404-410, https://doi.org/10.4161/nucl.21222.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Razin, S. V., and Gavrilov, A. A. (2014) Chromatin without the 30-nm fiber: constrained disorder instead of hierarchical folding, Epigenetics, 9, 653-657, https://doi.org/10.4161/epi.28297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Itoh, Y., Woods, E. J., Minami, K., Maeshima, K., and Collepardo-Guevara, R. (2021) Liquid-like chromatin in the cell: what can we learn from imaging and computational modeling?, Curr. Opin. Struct. Biol., 71, 123-135, https://doi.org/10.1016/j.sbi.2021.06.004.

    Article  CAS  PubMed  Google Scholar 

  103. Maeshima, K., Ide, S., Hibino, K., and Sasai, M. (2016) Liquid-like behavior of chromatin, Curr. Opin. Genet. Dev., 37, 36-45, https://doi.org/10.1016/j.gde.2015.11.006.

    Article  CAS  PubMed  Google Scholar 

  104. Nozaki, T., Kaizu, K., Pack, C. G., Tamura, S., Tani, T., et al. (2013) Flexible and dynamic nucleosome fiber in living mammalian cells, Nucleus, 4, 349-356, https://doi.org/10.4161/nucl.26053.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Hansen, J. C., Connolly, M., McDonald, C. J., Pan, A., Pryamkova, A., et al. (2018) The 10-nm chromatin fiber and its relationship to interphase chromosome organization, Biochem. Soc. Trans., 46, 67-76, https://doi.org/10.1042/BST20170101.

    Article  CAS  PubMed  Google Scholar 

  106. Allahverdi, A., Yang, R., Korolev, N., Fan, Y., Davey, C. A., et al. (2011) The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association, Nucleic Acids Res., 39, 1680-1691, https://doi.org/10.1093/nar/gkq900.

    Article  CAS  PubMed  Google Scholar 

  107. Laghmach, R., Di Pierro, M., and Potoyan, D. (2021) A liquid state perspective on dynamics of chromatin compartments, Front. Mol. Biosci., 8, 781981, https://doi.org/10.3389/fmolb.2021.781981.

    Article  CAS  PubMed  Google Scholar 

  108. Lee, R., Kang, M. K., Kim, Y. J., Yang, B., Shim, H., et al. (2022) CTCF-mediated chromatin looping provides a topological framework for the formation of phase-separated transcriptional condensates, Nucleic Acids Res., 50, 207-226, https://doi.org/10.1093/nar/gkab1242.

    Article  CAS  PubMed  Google Scholar 

  109. Rippe, K., and Papantonis, A. (2021) RNA polymerase II transcription compartments: from multivalent chromatin binding to liquid droplet formation?, Nat. Rev. Mol. Cell Biol., 22, 645-646, https://doi.org/10.1038/s41580-021-00401-6.

    Article  CAS  PubMed  Google Scholar 

  110. Razin, S. V., and Gavrilov, A. A. (2020) The role of liquid-liquid phase separation in the compartmentalization of cell nucleus and spatial genome organization, Biochemistry (Moscow), 85, 643-650, https://doi.org/10.1134/S0006297920060012.

    Article  CAS  Google Scholar 

  111. Hansen, J. C., Maeshima, K., and Hendzel, M. J. (2021) The solid and liquid states of chromatin, Epigenetics Chromatin, 14, 50, https://doi.org/10.1186/s13072-021-00424-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Strickfaden, H., Tolsma, T. O., Sharma, A., Underhill, D. A., Hansen, J. C., et al. (2020) Condensed chromatin behaves like a solid on the mesoscale in vitro and in living cells, Cell, 183, 1772-1784.e1713, https://doi.org/10.1016/j.cell.2020.11.027.

    Article  CAS  PubMed  Google Scholar 

  113. De Wit, E., and de Laat, W. (2012) A decade of 3C technologies: insights into nuclear organization, Genes Dev., 26, 11-24, https://doi.org/10.1101/gad.179804.111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., et al. (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre, Nature, 485, 381-385, https://doi.org/10.1038/nature11049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Dixon, J. R., Selvaraj, S., Yue, F., Kim, A., Li, Y., et al. (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions, Nature, 485, 376-380, https://doi.org/10.1038/nature11082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., et al. (2012) Three-dimensional folding and functional organization principles of the Drosophila genome, Cell, 148, 458-472, https://doi.org/10.1016/j.cell.2012.01.010.

    Article  CAS  PubMed  Google Scholar 

  117. Rao, S. S., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., et al. (2014) A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping, Cell, 159, 1665-1680, https://doi.org/10.1016/j.cell.2014.11.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Smeets, D., Markaki, Y., Schmid, V. J., Kraus, F., Tattermusch, A., et al. (2014) Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci, Epigenetics Chromatin, 7, 8, https://doi.org/10.1186/1756-8935-7-8.

    Article  PubMed  PubMed Central  Google Scholar 

  119. Cremer, T., Cremer, M., Hubner, B., Strickfaden, H., Smeets, D., et al. (2015) The 4D nucleome: Evidence for a dynamic nuclear landscape based on co-aligned active and inactive nuclear compartments, FEBS Lett., 589, 2931-2943, https://doi.org/10.1016/j.febslet.2015.05.037.

    Article  CAS  PubMed  Google Scholar 

  120. Szabo, Q., Jost, D., Chang, J. M., Cattoni, D. I., Papadopoulos, G. L., et al. (2018) TADs are 3D structural units of higher-order chromosome organization in Drosophila, Sci. Adv., 4, eaar8082, https://doi.org/10.1126/sciadv.aar8082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Bintu, B., Mateo, L. J., Su, J. H., Sinnott-Armstrong, N. A., Parker, M., et al. (2018) Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells, Science, 362, https://doi.org/10.1126/science.aau1783.

    Article  Google Scholar 

  122. Flyamer, I. M., Gassler, J., Imakaev, M., Brandao, H. B., Ulianov, S. V., et al. (2017) Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition, Nature, 544, 110-114, https://doi.org/10.1038/nature21711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Fudenberg, G., Imakaev, M., Lu, C., Goloborodko, A., Abdennur, N., et al. (2016) Formation of chromosomal domains by loop extrusion, Cell Rep., 15, 2038-2049, https://doi.org/10.1016/j.celrep.2016.04.085.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sanborn, A. L., Rao, S. S., Huang, S. C., Durand, N. C., Huntley, M. H., et al. (2015) Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes, Proc. Natl. Acad. Sci. USA, 112, E6456-6465, https://doi.org/10.1073/pnas.1518552112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Davidson, I. F., and Peters, J. M. (2021) Genome folding through loop extrusion by SMC complexes, Nat. Rev. Mol. Cell Biol., 22, 445-464, https://doi.org/10.1038/s41580-021-00349-7.

    Article  CAS  PubMed  Google Scholar 

  126. Cheutin, T., and Cavalli, G. (2014) Polycomb silencing: from linear chromatin domains to 3D chromosome folding, Curr. Opin. Genet. Dev., 25, 30-37, https://doi.org/10.1016/j.gde.2013.11.016.

    Article  CAS  PubMed  Google Scholar 

  127. Razin, S. V., and Gavrilov, A. A. (2021) Non-coding RNAs in chromatin folding and nuclear organization, Cell. Mol. Life Sci., 78, 5489-5504, https://doi.org/10.1007/s00018-021-03876-w.

    Article  CAS  PubMed  Google Scholar 

  128. Baudement, M. O., Cournac, A., Court, F., Seveno, M., Parrinello, H., et al. (2018) High-salt-recovered sequences are associated with the active chromosomal compartment and with large ribonucleoprotein complexes including nuclear bodies, Genome Res., 28, 1733-1746, https://doi.org/10.1101/gr.237073.118.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Ulianov, S. V., Khrameeva, E. E., Gavrilov, A. A., Flyamer, I. M., Kos, P., et al. (2016) Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains, Genome Res., 26, 70-84, https://doi.org/10.1101/gr.196006.115.

    Article  PubMed  PubMed Central  Google Scholar 

  130. Cremer, T., Cremer, M., and Cremer, C. (2018) The 4D nucleome: genome compartmentalization in an evolutionary context, Biochemistry (Moscow), 83, 313-325, https://doi.org/10.1134/S000629791804003X.

    Article  CAS  Google Scholar 

  131. Uusküla-Reimand, L., Hou, H., Samavarchi-Tehrani, P., Vietri Rudan, M., Liang, M., et al. (2016) Topoisomerase II beta interacts with cohesin and CTCF at topological domain borders, Genome Biol., 17, 182, https://doi.org/10.1186/s13059-016-1043-8.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Emerson, D. J., Zhao, P. A., Cook, A. L., Barnett, R. J., Klein, K. N., et al. (2022) Cohesin-mediated loop anchors confine the locations of human replication origins, Nature, 606, 812-819, https://doi.org/10.1038/s41586-022-04803-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Razin, S. V., Kekelidze, M. G., Lukanidin, E. M., Scherrer, K., and Georgiev, G. P. (1986) Replication origins are attached to the nuclear skeleton, Nucleic Acids Res., 14, 8189-8207, https://doi.org/10.1093/nar/14.20.8189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Micheli, G., Luzzatto, A. R., Carri, M. T., de Capoa, A., and Pelliccia, F. (1993) Chromosome length and DNA loop size during early embryonic development of Xenopus laevis, Chromosoma, 102, 478-483, https://doi.org/10.1007/BF00357103.

    Article  CAS  PubMed  Google Scholar 

  135. Naumova, N., Imakaev, M., Fudenberg, G., Zhan, Y., Lajoie, B. R., et al. (2013) Organization of the mitotic chromosome, Science, 342, 948-953, https://doi.org/10.1126/science.1236083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Golfier, S., Quail, T., Kimura, H., and Brugues, J. (2020) Cohesin and condensin extrude DNA loops in a cell cycle-dependent manner, Elife, 9, https://doi.org/10.7554/eLife.53885.

    Article  PubMed  PubMed Central  Google Scholar 

  137. Maeshima, K., and Laemmli, U. K. (2003) A two-step scaffolding model for mitotic chromosome assembly, Dev. Cell, 4, 467-480, https://doi.org/10.1016/s1534-5807(03)00092-3.

    Article  CAS  PubMed  Google Scholar 

  138. Meijering, A. E. C., Sarlos, K., Nielsen, C. F., Witt, H., Harju, J., et al. (2022) Nonlinear mechanics of human mitotic chromosomes, Nature, 605, 545-550, https://doi.org/10.1038/s41586-022-04666-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Mattern, K. A., Humbel, B. M., Muijsers, A. O., de Jong, L., and van Driel, R. (1996) hnRNP proteins and B23 are the major proteins of the internal nuclear matrix of HeLa S3 cells, J. Cell Biochem., 62, 275-289, https://doi.org/10.1002/(SICI)1097-4644(199608)62:2<275::AID-JCB15>3.0.CO;2-K.

    Article  CAS  PubMed  Google Scholar 

  140. Martelli, A. M., Manzoli, L., Rubbini, S., Billi, A. M., Bareggi, R., et al. (1995) The protein composition of Friend cell nuclear matrix stabilized by various treatments. Different recovery of nucleolar proteins B23 and C23 and nuclear lamins, Biol. Cell, 83, 15-22, https://doi.org/10.1016/0248-4900(96)89927-8.

    Article  CAS  PubMed  Google Scholar 

  141. Liao, Y., Zhang, X., Chakraborty, M., and Emerson, J. J. (2021) Topologically associating domains and their role in the evolution of genome structure and function in Drosophila, Genome Res., 31, 397-410, https://doi.org/10.1101/gr.266130.120.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Galupa, R., and Heard, E. (2017) Topologically associating domains in chromosome architecture and gene regulatory landscapes during development, disease, and evolution, Cold Spring Harb. Symp. Quant. Biol., 82, 267-278, https://doi.org/10.1101/sqb.2017.82.035030.

    Article  PubMed  Google Scholar 

  143. Krefting, J., Andrade-Navarro, M. A., and Ibn-Salem, J. (2018) Evolutionary stability of topologically associating domains is associated with conserved gene regulation, BMC Biol., 16, 87, https://doi.org/10.1186/s12915-018-0556-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Shrinivas, K., Sabari, B. R., Coffey, E. L., Klein, I. A., Boija, A., et al. (2019) Enhancer features that drive formation of transcriptional condensates, Mol. Cell, 75, 549-561.e547, https://doi.org/10.1016/j.molcel.2019.07.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Sabari, B. R., Dall’Agnese, A., Boija, A., Klein, I. A., Coffey, E. L., et al. (2018) Coactivator condensation at super-enhancers links phase separation and gene control, Science, 361, https://doi.org/10.1126/science.aar3958.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K., and Sharp, P. A. (2017) A phase separation model for transcriptional control, Cell, 169, 13-23, https://doi.org/10.1016/j.cell.2017.02.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Serebreni, L., and Stark, A. (2021) Insights into gene regulation: from regulatory genomic elements to DNA-protein and protein-protein interactions, Curr. Opin. Cell. Biol., 70, 58-66, https://doi.org/10.1016/j.ceb.2020.11.009.

    Article  CAS  PubMed  Google Scholar 

  148. Vernimmen, D., and Bickmore, W. A. (2015) The hierarchy of transcriptional activation: from enhancer to promoter, Trends Genet., 31, 696-708, https://doi.org/10.1016/j.tig.2015.10.004.

    Article  CAS  PubMed  Google Scholar 

  149. Mifsud, B., Tavares-Cadete, F., Young, A. N., Sugar, R., Schoenfelder, S., et al. (2015) Mapping long-range promoter contacts in human cells with high-resolution capture Hi-C, Nat. Genet., 47, 598-606, https://doi.org/10.1038/ng.3286.

    Article  CAS  PubMed  Google Scholar 

  150. Lupianez, D. G., Kraft, K., Heinrich, V., Krawitz, P., Brancati, F., et al. (2015) Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions, Cell, 161, 1012-1025, https://doi.org/10.1016/j.cell.2015.04.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Lupianez, D. G., Spielmann, M., and Mundlos, S. (2016) Breaking TADs: how alterations of chromatin domains result in disease, Trends Genet., 32, 225-237, https://doi.org/10.1016/j.tig.2016.01.003.

    Article  CAS  PubMed  Google Scholar 

  152. Franke, M., Ibrahim, D. M., Andrey, G., Schwarzer, W., Heinrich, V., et al. (2016) Formation of new chromatin domains determines pathogenicity of genomic duplications, Nature, 538, 265-269, https://doi.org/10.1038/nature19800.

    Article  CAS  PubMed  Google Scholar 

  153. Valton, A. L., and Dekker, J. (2016) TAD disruption as oncogenic driver, Curr. Opin. Genet. Dev., 36, 34-40, https://doi.org/10.1016/j.gde.2016.03.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Symmons, O., Uslu, V. V., Tsujimura, T., Ruf, S., Nassari, S., et al. (2014) Functional and topological characteristics of mammalian regulatory domains, Genome Res., 24, 390-400, https://doi.org/10.1101/gr.163519.113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Razin, S. V., and Ulianov, S. V. (2017) Gene functioning and storage within a folded genome, Cell. Mol. Biol. Lett., 22, 18, https://doi.org/10.1186/s11658-017-0050-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Dekker, J., and Heard, E. (2015) Structural and functional diversity of topologically associating domains, FEBS Lett., 589, 2877-2884, https://doi.org/10.1016/j.febslet.2015.08.044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Le Dily, F., Bau, D., Pohl, A., Vicent, G. P., Serra, F., et al. (2014) Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation, Genes Dev., 28, 2151-2162, https://doi.org/10.1101/gad.241422.114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Le Dily, F., and Beato, M. (2015) TADs as modular and dynamic units for gene regulation by hormones, FEBS Lett., 589, 2885-2892, https://doi.org/10.1016/j.febslet.2015.05.026.

    Article  CAS  PubMed  Google Scholar 

  159. Razin, S. V., Farrell, C. M., and Recillas-Targa, F. (2003) Genomic domains and regulatory elements operating at the domain level, Int. Rev. Cytol., 226, 63-125, https://doi.org/10.1016/s0074-7696(03)01002-7.

    Article  CAS  PubMed  Google Scholar 

  160. Recillas-Targa, F., and Razin, S. V. (2001) Chromatin domains and regulation of gene expression: familiar and enigmatic clusters of chicken globin genes, Crit. Rev. Eukaryot. Gene Expr., 11, 227-242, https://doi.org/10.1615/CritRevEukarGeneExpr.v11.i1-3.110.

    Article  CAS  PubMed  Google Scholar 

  161. Eres, I. E., and Gilad, Y. (2021) A TAD skeptic: is 3D genome topology conserved?, Trends Genet., 37, 216-223, https://doi.org/10.1016/j.tig.2020.10.009.

    Article  CAS  PubMed  Google Scholar 

  162. Ulianov, S. V., Zakharova, V. V., Galitsyna, A. A., Kos, P. I., Polovnikov, K. E., et al. (2021) Order and stochasticity in the folding of individual Drosophila genomes, Nat. Commun., 12, 41, https://doi.org/10.1038/s41467-020-20292-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. McCord, R. P., Nazario-Toole, A., Zhang, H., Chines, P. S., Zhan, Y., et al. (2013) Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson–Gilford progeria syndrome, Genome Res., 23, 260-269, https://doi.org/10.1101/gr.138032.112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Beccari, L., Jaquier, G., Lopez-Delisle, L., Rodriguez-Carballo, E., Mascrez, B., et al. (2021) Dbx2 regulation in limbs suggests interTAD sharing of enhancers, Dev. Dyn., 250, 1280-1299, https://doi.org/10.1002/dvdy.303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Dowen, J. M., Fan, Z. P., Hnisz, D., Ren, G., Abraham, B. J., et al. (2014) Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes, Cell, 159, 374-387, https://doi.org/10.1016/j.cell.2014.09.030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Hnisz, D., Day, D. S., and Young, R. A. (2016) Insulated neighborhoods: structural and functional units of mammalian gene control, Cell, 167, 1188-1200, https://doi.org/10.1016/j.cell.2016.10.024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Xiao, J. Y., Hafner, A., and Boettiger, A. N. (2021) How subtle changes in 3D structure can create large changes in transcription, Elife, 10, e64320, https://doi.org/10.7554/eLife.64320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Despang, A., Schopflin, R., Franke, M., Ali, S., Jerkovic, I., et al. (2019) Functional dissection of the Sox9-Kcnj2 locus identifies nonessential and instructive roles of TAD architecture, Nat. Genet., 51, 1263-1271, https://doi.org/10.1038/s41588-019-0466-z.

    Article  CAS  PubMed  Google Scholar 

  169. Nora, E. P., Goloborodko, A., Valton, A. L., Gibcus, J. H., Uebersohn, A., et al. (2017) Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization, Cell, 169, 930-944.e922, https://doi.org/10.1016/j.cell.2017.05.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Schwarzer, W., Abdennur, N., Goloborodko, A., Pekowska, A., Fudenberg, G., et al. (2017) Two independent modes of chromatin organization revealed by cohesin removal, Nature, 551, 51-56, https://doi.org/10.1038/nature24281.

    Article  PubMed  PubMed Central  Google Scholar 

  171. Rao, S. S. P., Huang, S. C., Glenn St Hilaire, B., Engreitz, J. M., Perez, E. M., et al. (2017) Cohesin loss eliminates all loop domains, Cell, 171, 305-320.e324, https://doi.org/10.1016/j.cell.2017.09.026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Zuin, J., Dixon, J. R., van der Reijden, M. I., Ye, Z., Kolovos, P., et al. (2014) Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells, Proc. Natl. Acad. Sci. USA, 111, 996-1001, https://doi.org/10.1073/pnas.1317788111.

    Article  CAS  PubMed  Google Scholar 

  173. Hanssen, L. L. P., Kassouf, M. T., Oudelaar, A. M., Biggs, D., Preece, C., et al. (2017) Tissue-specific CTCF-cohesin-mediated chromatin architecture delimits enhancer interactions and function in vivo, Nat. Cell Biol., 19, 952-961, https://doi.org/10.1038/ncb3573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Ulianov, S. V., Galitsyna, A. A., Flyamer, I. M., Golov, A. K., Khrameeva, E. E., et al. (2017) Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure, Epigenetics Chromatin, 10, 35, https://doi.org/10.1186/s13072-017-0142-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The study was carried out within the framework of the Interdisciplinary Scientific and Educational School of Moscow University “Molecular Technologies of Living Systems and Synthetic Biology”.

Funding

The work of S. V. Razin and O. L. Kantidze was supported by the Russian Science Foundation (project no. 21-64-00001). The work of I. V. Zhegalova was supported by the Russian Foundation for Basic Research (project no. 20-34-90058).

Author information

Authors and Affiliations

  1. Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    Sergey V. Razin & Omar L. Kantidze

  2. Faculty of Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    Sergey V. Razin

  3. Skolkovo Institute of Science and Technology, 121205, Moscow, Russia

    Irina V. Zhegalova

  4. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991, Moscow, Russia

    Irina V. Zhegalova

  5. Kharkevich Institute for Information Transmission Problems, 127051, Moscow, Russia

    Irina V. Zhegalova

Authors
  1. Sergey V. Razin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irina V. Zhegalova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Omar L. Kantidze
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors participated in the development of the concept and writing the review.

Corresponding author

Correspondence to Sergey V. Razin.

Ethics declarations

The authors declare no conflicts of interest. This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Razin, S.V., Zhegalova, I.V. & Kantidze, O.L. Domain Model of Eukaryotic Genome Organization: From DNA Loops Fixed on the Nuclear Matrix to TADs. Biochemistry Moscow 87, 667–680 (2022). https://doi.org/10.1134/S0006297922070082

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297922070082

Keywords

Search

Navigation