Аннотация

The increasing variability of phenotypic traits in agricultural animal species makes it necessary to search for reliable DNA markers. Due to the poor efficiency of using clustered single-nucleotide polymorphisms (SNP) and individual genomic elements, the hierarchy of gene regulatory networks has become a relevant research area. We summarized available information on different levels of epigenetic regulation, from the linear DNA sequence and its secondary and tertiary structures to the factors outside the cell nucleus, i.e., intercellular contacts and interactions with the extracellular matrix. We also discussed the features of genomic distribution and the role of topologically associated domains (TADs), and architectural protein CTCF in chromatin loop formation. CTCF mediates protein-protein interactions and interacts with various RNA variants. It also involved in epigenetic modifications of the DNA nucleotide sequence, a target of CTCF binding. Such targeted sites are located in transposable elements (TEs). As a result of the evolutionary conservation, they are also to be found in TAD, regardless of the fact that they are delivered by species-specific TEs. CTCF and its binding sites are known to affect the structure of the mitotic spindle. They also have a certain impact on cholesterol biosynthesis, which affects the plasma membrane and cell migration. CTCF indirectly participates in the variability of intercellular contacts and interactions with the extracellular matrix. In animals, CTCF and its binding targets are involved in all levels of gene regulatory networks that maintain or change genomic expression.

Ключевые слова

G4 quadruplexes, DNA-RNA hybrids, CTCF, chromatin loops, topologically associated domains (TAD), extranuclear factors, neoplastic transformation

ФИНАНСИРОВАНИЕ

The study is supported by the Ministry of Science and Higher Education of the Russian Federation (state agreement No. 075-00503-24-01).

СПИСОК ЛИТЕРАТУРЫ

1. Glazko VI, Kosovsky GYu, Glazko TT. The Sources of Genome Variability as Domestication Drivers (Review). Agricultural Biology. 2022;57(5):832–851. (In Russ.). https://doi.org/10.15389/agrobiology.2022.5.832rus
2. Glazko VI, Kosovsky GYu, Glazko TT, Fedorova LM. DNA Markers and Microsatellite Code (Review). Agricultural Biology. 2023;58(2):223–248. (In Russ.). https://doi.org/10.15389/agrobiology.2023.2.223rus
3. Choudhary MNK, Quaid K, Xing X, Schmidt H, Wang T. Widespread Contribution of Transposable Elements to The Rewiring of Mammalian 3D Genomes. Nature Communications. 2023;14:634. https://doi.org/10.1038/s41467-023-36364-9
4. Gebrie A. Transposable Elements as Essential Elements in The Control of Gene Expression. Mobile DNA. 2023;14:9. https://doi.org/10.1186/s13100-023-00297-3
5. Lawson HA, Liang Y, Wang T. Transposable Elements in Mammalian Chromatin Organization. Nature Reviews Genetics. 2023;24:712–723. https://doi.org/10.1038/S41576-023-00609-6
6. Lu JY, Chang L, Li T, Wang T, Yin Y, Zhan G, et al. Homotypic Clustering of L1 and B1/Alu Repeats Compartmentalizes the 3D Genome. Cell Research. 2021;31:613–630. https://doi.org/10.1038/s41422-020-00466-6
7. Glazko TT, Glazko GV, Kosovsky GYu, Zybaylov VL, Glazko VI. Interphase Nucleus and Transposable Elements (Review). Biogeosystem Technique. 2022;(9):62–76. (In Russ.). https://doi.org/10.13187/bgt.2022.2.62
8. Mustafin RN. A Hypothesis about Interrelations of Epigenetic Factors and Transposable Elements in Memory Formation. Vavilov Journal of Genetics and Breeding. 2024;28(5):476–486. (In Russ.). https://doi.org/10.18699/vjgb-24-54
9. Hubert JN, Perret M, Riquet J, Demars J. Livestock Species as Emerging Models for Genomic Imprinting. Frontiers in Cell and Developmental Biology. 2024;12:1348036. https://doi.org/10.3389/fcell.2024.1348036
10. Strahl BD, Allis CD. The Language of Covalent Histone Modifications. Nature. 2000;403:41–45. https://doi.org/10.1038/47412
11. Falk M, Feodorova Y, Naumova N, Imakaev M, Lajoie BR, Leonhardt H, et al. Heterochromatin Drives Compartmentalization of Inverted and Conventional Nuclei. Nature. 2018;570:395–399. https://doi.org/10.1101/244038
12. Glaser J, Mundlos S. 3D or Not 3D: Shaping the Genome during Development. Cold Spring Harbor Perspectives in Biology. 2022;14:a040188. https://doi.org/10.1101/cshperspect.a040188
13. Gamliel A, Meluzzi D, Oh S, Jiang N, Destici E, Rosenfeld MG, et al. Long-Distance Association of Topological Boundaries Through Nuclear Condensates. Proceedings of the National Academy of Sciences. 2022;119(32):e2206216119. https://doi.org/10.1073/pnas.2206216119
14. Abnizova I, Stapel C, Boekhorst RT, Lee JTH, Hemberg M. Integrative Analysis of Transcriptomic and Epigenomic Data Reveals Distinct Patterns for Developmental and Housekeeping Gene Regulation. BMC Biology. 2024;22:78. https://doi.org/10.1186/s12915-024-01869-2
15. Gheldof N, Witwicki RM, Migliavacca E, Leleu M, Didelot G, Harewood L, et al. Structural Variation-Associated Expression Changes are Paralleled by Chromatin Architecture Modifications. PLoS One. 2013;8(11):e79973. https://doi.org/10.1371/journal.pone.0079973
16. Magnitov M, de Wit E. (2024) Attraction and Disruption: How Loop Extrusion and Compartmentalisation Shape the Nuclear Genome. Current Opinion in Genetics and Development. 2024;86:102194. https://doi.org/10.1016/j.gde.2024.102194
17. Logie C. The Role of CTCF-Mediated Chromatin Looping in Enhancer-Promoter Communication. In: Witzany G, editor. Epigenetics in Biological Communication. Springer: Cham; 2024. pp. 333–355. https://doi.org/10.1007/978-3-031-59286-7_16
18. Behrends M, Engmann O. Loop Interrupted: Dysfunctional Chromatin Relations in Neurological Diseases. Frontiers in Genetics. 2021;12:732033. https://doi.org/10.3389/fgene.2021.732033
19. Osman N, Shawky AE, Brylinski M. Exploring the Effects of Genetic Variation on Gene Regulation in Cancer in The Context Of 3D Genome Structure. BMC Genomic Data. 2022;23:13. https://doi.org/10.1186/s12863-021-01021-x
20. Mitchell AC, Bharadwaj R, Whittle C, Krueger W, Mirnics K, Hurd Y, et al. The Genome in Three Dimensions: A New Frontier in Human Brain Research. Biological Psychiatry. 2014;75(12);961–969. https://doi.org/10.1016/j.biopsych.2013.07.015
21. Lobanenkov VV, Nicolas RH, Adler VV, Paterson H, Klenova EM, Polotskaja AV, et al. A Novel Sequence-Specific DNA Binding Protein Which Interacts with Three Regularly Spaced Direct Repeats of the CCCTC-Motif in the 5'-Flanking Sequence of the Chicken C-Myc Gene. Oncogene. 1990;5(12):1743–1753.
22. Maksimenko OG, Fursenko DV, Belova EV, Georgiev PG. CTCF As an Example of DNA-Binding Transcription Factors Containing Clusters of C2H2-Type Zinc Fingers. Acta Naturae. 2021;13(1):31–46. (In Russ.). https://doi.org/10.32607/actanaturae.11206
23. Del Moral-Morales A, Salgado-Albarrán M, Sánchez-Pérez Y, Wenke NK, Baumbach J, Soto-Reyes E. CTCF and Its Multi-Partner Network for Chromatin Regulation. Cells. 2023;12(10):1357. https://doi.org/10.3390/cells12101357
24. Tang X, Zeng P, Liu K, Qing L, Sun Y, Liu X, et al. The PTM Profiling of CTCF Reveals the Regulation of 3D Chromatin Structure by O-Glcnacylation. Nature Communications. 2024;15:2813. https://doi.org/10.1038/s41467-024-47048-3
25. Wang J, Vicente-García C, Seruggia D, Moltó E, Fernandez-Miñán A, Neto A, et al. MIR Retrotransposon Sequences Provide Insulators to the Human Genome. Proceedings of the National Academy of Sciences. 2015; 112(32):E4428–E4437. https://doi.org/10.1073/pnas.1507253112
26. Tian H, Luan P, Liu Y, Li G. Tet-mediated DNA Methylation Dynamics Affect Chromosome Organization. Nucleic Acids Research. 2024;52(4):3654–3666. https://doi.org/10.1093/nar/gkae054
27. Razin SV, Gavrilov AA. Non-coding RNAs in Chromatin Folding and Nuclear Organization. Cellular and Molecular Life Sciences. 2021;78:5489–5504. https://doi.org/10.1007/s00018-021-03876-w
28. Soibam B. Association between Triplex-Forming Sites of Cardiac Long Noncoding RNA GATA6-AS1 and Chromatin Organization. Non-coding RNA. 2022;8(13):41. https://doi.org/10.3390/ncrna8030041
29. Zacco E, Broglia L, Kurihara M, Monti M, Gustincich S, Pastore A, Plath K, et al. RNA: The Unsuspected Conductor in the Orchestra of Macromolecular Crowding. Chemical Reviews. 2024;124(8):4734–4777. https://doi.org/10.1021/acs.chemrev.3c00575
30. Poller W, Sahoo S, Hajjar R, Landmesser U, Krichevsky AM. Exploration of the Noncoding Genome for Human-Specific Therapeutic Targets-Recent Insights at Molecular and Cellular Level. Cells. 2023;12(22):2660. https://doi.org/10.3390/cells12222660
31. Merici G, Amidani D, Dieci G, Rivetti C. A New Strategy to Investigate RNA: DNA Triplex Using Atomic Force Microscopy. International Journal of Molecular Sciences. 2024;25(5):3035. https://doi.org/10.3390/ijms25053035
32. Zhang H, Shi Z, Banigan EJ, Kim Y, Yu H, Bai XC, et al. CTCF and R-loops are Boundaries of Cohesin-Mediated DNA Looping. Molecular Cell. 2023;83(16):2856–2871. https://doi.org/10.1016/j.molcel.2023.07.006
33. Wulfridge P, Yan Q, Rell N, Doherty J, Jacobson S, Offley S, et al. G-quadruplexes Associated with R-loops Promote CTCF Binding. Molecular Cell. 2023;83(17):3064–3079. https://doi.org/10.1016/j.molcel.2023.07.009
34. Hou Y, Li F, Zhang R, Li S, Liu H, Qin ZS, Sun X. Integrative Characterization of G-Quadruplexes in the Three-Dimensional Chromatin Structure. Epigenetics. 2019;14(9):894–911. https://doi.org/10.1080/15592294.2019.1621140
35. Moindrot B, Imaizumi Y, Feil R. Differential 3D Genome Architecture and Imprinted Gene Expression: Cause or Consequence? Biochemical Society Transactions. 2024;52(3):973–986. https://doi.org/10.1042/BST20230143
36. Gómez-Redondo I, Planells B, Cánovas S, Ivanova E, Kelsey G, Gutiérrez-Adán A. Genome-wide DNA Methylation Dynamics During Epigenetic Reprogramming in The Porcine Germline. Clinical Epigenetics. 2021;13:27. https://doi.org/10.1186/s13148-021-01003-x
37. Noordermeer D, Feil R. Differential 3D Chromatin Organization and Gene Activity in Genomic Imprinting. Current Opinion in Genetics and Development. 2020;61:17–24. https://doi.org/10.1016/j.gde.2020.03.004
38. Monk, D, Mackay DJG, Eggermann T, Maher ER, Riccio A. Genomic Imprinting Disorders: Lessons on How Genome, Epigenome and Environment Interact. Nature Reviews Genetics. 2019;20:235–248. https://doi.org/10.1038/s41576-018-0092-0
39. Hubert J-N, Demars J. Genomic Imprinting in The New Omics Era: A Model for Systems-Level Approaches. Frontiers in Genetics. 2022;13:838534. https://doi.org/10.3389/fgene.2022.838534
40. MacDonald WA, Mann MRW. Long Noncoding RNA Functionality in Imprinted Domain Regulation. PLOS Genetics. 2020;16(8):e1008930. https://doi.org/10.1371/journal.pgen.1008930
41. Malnou EC, Umlauf D, Mouysset M, Cavaillé J. Imprinted MicroRNA Gene Clusters in The Evolution, Development, and Functions of Mammalian Placenta. Frontiers in Genetics. 2019;9:706. https://doi.org/10.3389/fgene.2018.00706
42. Sanli I, Feil R. Chromatin Mechanisms in the Developmental Control of Imprinted Gene Expression. The International Journal of Biochemistry and Cell Biology. 2015;67:139–147. https://doi.org/10.1016/j.biocel.2015.04.004
43. Choudhary MN, Friedman RZ, Wang JT, Jang HS, Zhuo X, Wang T. Co-opted Transposons Help Perpetuate Conserved Higher-Order Chromosomal Structures. Genome Biology. 2020;21:16. https://doi.org/10.1186/s13059-019-1916-8
44. Buckley RM, Kortschak RD, Raison JM, Adelson DL. Similar Evolutionary Trajectories for Retrotransposon Accumulation in Mammals. Genome Biology and Evolution. 2017;9(9):2336–2353. https://doi.org/10.1093/gbe/evx179
45. DiRusso JA, Clark AT. Transposable Elements in Early Human Embryo Development and Embryo Models. Current Opinion in Genetics and Development. 2023;81:102086. https://doi.org/10.1016/j.gde.2023.102086
46. Zhao P, Peng C, Fang L, Wang Z, Liu GE. Taming Transposable Elements in Livestock and Poultry: A Review of Their Roles and Applications. Genetics Selection Evolution. 2023;55:50. https://doi.org/10.1186/s12711-023-00821-2
47. Wang M, Hancock TP, Chamberlain AJ, Vander Jagt CJ, Pryce JE, Cocks BG, et al. Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits. BMC Genomics. 2018;19:395. https://doi.org/10.1101/242792
48. Engmann O, Labonté B, Mitchell A, Bashtrykov P, Calipari ES, Rosenbluh C, et al. Cocaine-Induced Chromatin Modifications Associate with Increased Expression and Three-Dimensional Looping of Auts2. Biological Psychiatry. 2017;82(11):794–805. https://doi.org/10.1016/j.biopsych.2017.04.013
49. Szabó D, Franke V, Bianco S, Batiuk MY, Paul EJ, Kukalev A, et al. A Single Dose of Cocaine Rewires The 3D Genome Structure of Midbrain Dopamine Neurons. 2024. https://doi.org/10.1101/2024.05.10.593308
50. Tashiro S, Lanctôt C. The International Nucleome Consortium. Nucleus. 2015;6(2):89–92. https://doi.org/10.1080/19491034.2015.1022703
51. Rey-Millet M, Bystricky K.International Nucleome Consortium. The Genome in Space and Time Comes of Age. Nucleus. 2024;15(2):2307665. https://doi.org/10.1080/19491034.2024.2307665
52. Huang H, Wu Q. Pushing the TAD Boundary: Decoding Insulator Codes of Clustered CTCF Sites in 3D Genomes. BioEssays. 2024;46(10):2400121. https://doi.org/10.1002/bies.202400121
53. Sandoval-Velasco M, Dudchenko O, Rodríguez JA, Pérez Estrada C, Dehasque M, Fontsere C, et al. Three-Dimensional Genome Architecture Persists in a 52,000-Year-Old Woolly Mammoth Skin Sample. Cell. 2024;187(14):3541–3562. https://doi.org/10.1016/j.cell.2024.06.002
54. Chen Z, Snetkova V, Bower G, Jacinto S, Clock B, Dizehchi A, et al. Increased Enhancer-Promoter Interactions During Developmental Enhancer Activation in Mammals. Nature Genetics. 2024;56:675–685. https://doi.org/10.1038/s41588-024-01681-2
55. Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, et al. Preferential Associations between Co-Regulated Genes Reveal a Transcriptional Interactome in Erythroid Cells. Nature Genetics. 2010;42:53–61. https://doi.org/10.1038/ng.496
56. Yan Y, Tian Y, Wu Z, Zhang K, Yang R. Interchromosomal Colocalization with Parental Genes Is Linked to the Function and Evolution of Mammalian Retrocopies. Molecular Biology and Evolution. 2023;40(12):msad265. https://doi.org/10.1093/molbev/msad265
57. Pollex T, Marco-Ferreres R, Ciglar L, Ghavi-Helm Y, Rabinowitz A, Viales RR, et al. Chromatin Gene-Gene Loops Support the Cross-Regulation of Genes with Related Function. Molecular Cell. 2024;84(15):822–838. https://doi.org/10.1016/j.molcel.2023.12.023
58. Fudenberg G, Kelley DR, Pollard KS. Predicting 3D Genome Folding from DNA Sequence with Akita. Nature Methods. 2020;17:1111–1117. https://doi.org/10.1038/s41592-020-0958-x
59. Liu T, Zhu H, Wang Z. Learning Micro-C from Hi-C with Diffusion Models. PLoS Computational Biology. 2024;20(5):e1012136. https://doi.org/10.1371/journal.pcbi.1012136
60. Keough KC, Whalen S, Inoue F, Przytycki PF, Fair T, Deng C, et al. Three-Dimensional Genome Rewiring in Loci with Human Accelerated Regions. Science. 2023;380:(6643):eabm1696. https://doi.org/10.1126/science.abm1696
61. Braunger JM, Cammarata LV, Sornapudi TR, Uhler C, Shivashankar GV. Transcriptional Changes Are Tightly Coupled to Chromatin Reorganization During Cellular Aging. Aging Cell. 2024;23(3):e14056. https://doi.org/10.1111/acel.14056
62. Schmitt AD, Sikkink K, Ahmed AA, Melnyk S, Reid D, Van Meter L, et al. Evaluation of Hi-C Sequencing for the Detection of Gene Fusions in Hematologic and Solid Pediatric Cancer Samples. Cancers. 2024;16(170:2936. https://doi.org/10.3390/cancers16172936
63. Glazko TT. Approaches to the Analysis of Reciprocal Chromosome Distribution in the Bone Marrow Cells of Mice. Tsitologiya. 1988;30(5):597–605. (In Russ.). https://elibrary.ru/UWLSHL
64. Righolt CH, Wiener F, Taylor-Kashton C, Harizanova J, Vermolen BJ, Garini Y, et al. Translocation Frequencies and Chromosomal Proximities for Selected Mouse Chromosomes in Primary B Lymphocytes. Cytometry. 2011;79A(4):276–283. https://doi.org/10.1002/cyto.a.21038
65. Kovalchuk AL, Kim JS, Janz S. Eμ/Sμ Transposition into Myc is Sometimes a Precursor for T(12;15) Translocation in Mouse B Cells. Oncogene. 2003;22:2842–2850. https://doi.org/10.1038/sj.onc.1206345
66. McStay B. Nucleolar Organizer Regions: Genomic 'Dark Matter' Requiring Illumination. Genes Development. 2016;30:1598–1610. https://doi.org/10.1101/gad.283838.116
67. Monahan K, Schieren I, Cheung J, Mumbey-Wafula A, Monuki ES, Lomvardas S. Cooperative Interactions Enable Singular Olfactory Receptor Expression in Mouse Olfactory Neurons. Elife. 2017;6:e28620. https://doi.org/10.7554/eLife.28620
68. Gamliel A, Meluzzi D, Oh S, Jiang N, Destici E, Rosenfeld MG, et al. Long-distance association of Topological Boundaries Through Nuclear Condensates. Proceedings of the National Academy of Sciences. 2022;1199320;e2206216119. https://doi.org/10.1073/pnas.2206216119
69. Ozery-Flato M, Linhart C, Trakhtenbrot L, Izraeli S, Shamir R. Large-Scale Analysis of Chromosomal Aberrations in Cancer Karyotypes Reveals Two Distinct Paths to Aneuploidy. Genome Biology. 2011;12:R61. https://doi.org/10.1186/gb-2011-12-6-r61
70. Maass PG, Barutcu AR, Weiner CL, Rinn JL. Inter-chromosomal Contact Properties in Live-Cell Imaging and in Hi-C. Molecular Cell. 2018;69(15):1039–1045. https://doi.org/10.1016/j.molcel.2018.02.007
71. Maass PG, Barutcu AR, Rinn JL. Interchromosomal Interactions: A Genomic Love Story of Kissing Chromosomes. Journal of Cell Biology. 2019;218(1):27–38. https://doi.org/10.1083/jcb.201806052
72. Roller M, Stamper E, Villar D, Izuogu O, Martin F, Redmond AM, et al. LINE Retrotransposons Characterize Mammalian Tissue-Specific and Evolutionarily Dynamic Regulatory Regions. Genome Biology. 2021;22:62. https://doi.org/10.1186/s13059-021-02260-y
73. James C, Trevisan-Herraz M, Juan D, Rico D. Evolutionary Analysis of Gene Ages Across Tads Associates Chromatin Topology with Whole-Genome Duplications. Cell Reports. 2024;43(4):113895. https://doi.org/10.1016/j.celrep.2024.113895
74. Fernandez MK, Sinha M, Zidan M, Renz M. Nuclear Actin Filaments – a Historical Perspective. Nucleus. 2024;15(1):2320656. https://doi.org/10.1080/19491034.2024.2320656
75. Venit T, Xie X, Percipalle P. Actin in the Cell Nucleus. In: Victor JM, editor. Nuclear Architecture and Dynamics. Boston: Academic Press; 2018. p 345–367.
76. Mahmood SR, Xie X, Hosny El Said N, Venit T, Gunsalus KC, Percipalle P. β-actin Dependent Chromatin Remodeling Mediates Compartment Level Changes in 3D Genome Architecture. Nature Communications. 2021;12:5240. https://doi.org/10.1038/s41467-021-25596-2
77. Wollscheid HP, Ulrich HD. Chromatin Meets the Cytoskeleton: The Importance of Nuclear Actin Dynamics and Associated Motors for Genome Stability. DNA Repair. 2023;131:103571. https://doi.org/10.1016/j.dnarep.2023.103571
78. Sen B, Xie Z, Thomas MD, Pattenden SG, Howard S, McGrath C, et al. Nuclear Actin Structure Regulates Chromatin Accessibility. Nature Communications. 2024;15:4095. https://doi.org/10.1038/s41467-024-48580-y
79. Zhuo L, Stöckl JB, Fröhlich T, Moser S, Vollmar AM, Zahler S. A Novel Interaction of Slug (SNAI2) and Nuclear Actin. Cells. 2024;13(8):696. https://doi.org/10.3390/cells13080696
80. Marshall-Burghardt S, Migueles-Ramírez RA, Lin Q, El Baba N, Saada R, Umar M, Mavalwala K, et al. Excitable Rho Dynamics Control Cell Shape and Motility by Sequentially Activating ERM Proteins and Actomyosin Contractility. Science Advances. 2024;10(36):eadn6858. https://doi.org/10.1126/sciadv.adn6858
81. Chiu K, Berrada Y, Eskndir N, Song D, Fong C, Naughton S, et al. CTCF is Essential for Proper Mitotic Spindle Structure and Anaphase Segregation. Chromosoma. 2024;133:183–194. https://doi.org/10.1007/s00412-023-00810-w
82. Kaczmarczyk LS, Levi N, Salmon-Divon M, Gerlitz G. The CTCF-H3K27me3 Axis Supports Melanoma Cell Migration by Repressing Cholesterol Biosynthesis. 2023. https://doi.org/10.1101/2023.02.23.529650
83. Lee K, Nelson CM. New Insights into The Regulation of Epithelial-Mesenchymal Transition and Tissue Fibrosis. International Review of Cell and Molecular Biology. 2012;294:171–221. https://doi.org/10.1016/B978-0-12-394305-7.00004-5
84. Andrianto A, Sudiana IK, Suprabawati DGA. α-Smooth Muscle Actin as Predictors of Early Recurrence in Early-Stage Ductal Type Breast Cancer After Mastectomy and Chemotherapy. Iranian Journal Pathology. 2024;19(1):67–74. https://doi.org/10.30699/ijp.2023.2004468.3126
85. Doll S, Freitas FP, Shah R, Aldrovandi M, da Silva MC, Ingold I, et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019;575:693–698. https://doi.org/10.1038/s41586-019-1707-0
86. Chao S, Yan H, Bu P. Asymmetric Division of Stem Cells and its Cancer Relevance. Cell Regeneration. 2024;13:5. https://doi.org/10.1186/s13619-024-00188-9
87. Baker SG, Soto AM, Sonnenschein C, Cappuccio A, Potter JD, Kramer BS. Plausibility of Stromal Initiation of Epithelial Cancers Without a Mutation in The Epithelium: A Computer Simulation of Morphostats. BMC Cancer. 2009;9:89. https://doi.org/10.1186/1471-2407-9-89
88. Zhu S, Wang J, Zellmer L, Xu N, Liu M, Hu Y, et al. Mutation or Not, What Directly Establishes a Neoplastic State, Namely Cellular Immortality and Autonomy, Still Remains Unknown and Should Be Prioritized in Our Research. Journal of Cancer. 2022;13(9):2810–2843. https://doi.org/10.7150/jca.72628
89. Berenblum I, Shubik P. An Experimental Study of The Initiating State of Carcinogenesis, and a Re-Examination of The Somatic Cell Mutation Theory of Cancer. British Journal of Cancer. 1949;3(1):109–118. https://doi.org/10.1038/bjc.1949.13
90. Foulds L. Multiple etiologic factors in neoplastic development. Cancer Research.1965;25(8):1339–1347.
91. Finn EH, Pegoraro G, Brandão HB, Valton AL, Oomen ME, Dekker J, et al. Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization. Cell. 2019;176(6):1502–1515. https://doi.org/10.1016/j.cell.2019.01.020
92. Ayyamperumal P, Naik HC, Naskar AJ, Bammidi LS, Gayen S. Epigenomic States Contribute to Coordinated Allelic Transcriptional Bursting in iPSC reprogramming. Life Science Alliance. 2024;7(4):e202302337. https://doi.org/10.26508/lsa.202302337
93. Glazko TT, Glazko VI. Segregation Of Haploid Sets of Chromosomes in Diploid Cells of a Number of Mammalian Species. Cifra. Biology. 2024;2:2. (In Russ.). https://doi.org/10.60797/BIO.2024.2.1
94. Mikhalchenko A, Gutierrez NM, Frana D, Safaei Z, Van Dyken C, Li Y, et al. Induction of Somatic Cell Haploidy by Premature Cell Division. Science Advances. 2024;10(10):eadk9001. https://doi.org/10.1126/sciadv.adk9001
95. Cho CJ, Brown JW, Mills JC. Origins of Cancer: Ain't It Just Mature Cells Misbehaving? EMBO Journal. 2024;43(13):2530–2551.
96. Markert CL. Neoplasia: a disease of cell differentiation. Cancer Research. 1968;28(9):1908–1914.
97. Trivedi DD, Dalai SK, Bakshi SR. The Mystery of Cancer Resistance: A Revelation Within Nature. Journal of Molecular Evolution. 2023;91:133–155. https://doi.org/10.1007/s00239-023-10092-6