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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Interplay between epigenome and 3D chromatin structure

  • Man-Hyuk Han (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Dariya Issagulova (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Minhee Park (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST))
  • Received : 2023.10.19
  • Accepted : 2023.12.05
  • Published : 2023.12.31
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Abstract

Epigenetic mechanisms, primarily mediated through histone and DNA modifications, play a pivotal role in orchestrating the functional identity of a cell and its response to environmental cues. Similarly, the spatial arrangement of chromatin within the three-dimensional (3D) nucleus has been recognized as a significant factor influencing genomic function. Investigating the relationship between epigenetic regulation and 3D chromatin structure has revealed correlation and causality between these processes, from the global alignment of average chromatin structure with chromatin marks to the nuanced correlations at smaller scales. This review aims to dissect the biological significance and the interplay between the epigenome and 3D chromatin structure, while also exploring the underlying molecular mechanisms. By synthesizing insights from both experimental and modeling perspectives, we seek to provide a comprehensive understanding of cellular functions.

Keywords

Acknowledgement

This work was supported by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF2022R1A5A102641311), NRF-2022R1C1C1004100, NRF-2019R1A6A1A10073887, KAIST UP Program, POSCO Science Fellowship of POSCO TJ Park Foundation.

References

  1. Waterland RA (2006) Epigenetic mechanisms and gastrointestinal development. J Pediatr 149, S137-S142  https://doi.org/10.1016/j.jpeds.2006.06.064
  2. Gibney ER and Nolan CM (2010) Epigenetics and gene expression. Heredity 105, 4-13  https://doi.org/10.1038/hdy.2010.54
  3. Kornberg RD and Lorch Y (1999) Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98, 285-294  https://doi.org/10.1016/S0092-8674(00)81958-3
  4. Luger K, Mader AW, Richmond RK, Sargent DF and Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251-260  https://doi.org/10.1038/38444
  5. Kouzarides T (2007) Chromatin modifications and their function. Cell 128, 693-705  https://doi.org/10.1016/j.cell.2007.02.005
  6. Bannister AJ and Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21, 381-395  https://doi.org/10.1038/cr.2011.22
  7. Quina AS, Buschbeck M and Di Croce L (2006) Chromatin structure and epigenetics. Biochem Pharmacol 72, 1563-1569  https://doi.org/10.1016/j.bcp.2006.06.016
  8. Moore LD, Le T and Fan G (2013) DNA methylation and its basic function. Neuropsychopharmacology 38, 23-38  https://doi.org/10.1038/npp.2012.112
  9. Gillette TG and Hill JA (2015) Readers, writers, and erasers: chromatin as the whiteboard of heart disease. Circ Res 116, 1245-1253  https://doi.org/10.1161/CIRCRESAHA.116.303630
  10. Vermeulen M, Mulder KW, Denissov S et al (2007) Selective anchoring of TFIID to nucleosomes by trimethylation of histone H3 lysine 4. Cell 131, 58-69  https://doi.org/10.1016/j.cell.2007.08.016
  11. Shi J and Vakoc Christopher R (2014) The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell 54, 728-736  https://doi.org/10.1016/j.molcel.2014.05.016
  12. Millan-Zambrano G, Burton A, Bannister AJ and Schneider R (2022) Histone post-translational modifications - cause and consequence of genome function. Nat Rev Genet 23, 563-580  https://doi.org/10.1038/s41576-022-00468-7
  13. Tamaru H (2010) Confining euchromatin/heterochromatin territory: jumonji crosses the line. Genes Dev 24, 1465-1478  https://doi.org/10.1101/gad.1941010
  14. Padeken J, Methot SP and Gasser SM (2022) Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance. Nat Rev Mol Cell Biol 23, 623-640  https://doi.org/10.1038/s41580-022-00483-w
  15. Gonzalez-Sandoval A, Towbin BD, Kalck V et al (2015) Perinuclear anchoring of H3K9-methylated chromatin stabilizes induced cell fate in C. elegans embryos. Cell 163, 1333-1347  https://doi.org/10.1016/j.cell.2015.10.066
  16. Lieberman-Aiden E, van Berkum NL, Williams L et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289-293  https://doi.org/10.1126/science.1181369
  17. Bonev B and Cavalli G (2016) Organization and function of the 3D genome. Nat Rev Genet 17, 661-678  https://doi.org/10.1038/nrg.2016.112
  18. Leidescher S, Ribisel J, Ullrich S et al (2022) Spatial organization of transcribed eukaryotic genes. Nat Cell Biol 24, 327-339  https://doi.org/10.1038/s41556-022-00847-6
  19. Osborne CS, Chakalova L, Brown KE et al (2004) Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36, 1065-1071  https://doi.org/10.1038/ng1423
  20. Bickmore WA (2013) The spatial organization of the human genome. Annu Rev Genomics Hum Genet 14, 67-84  https://doi.org/10.1146/annurev-genom-091212-153515
  21. Wang S, Su JH, Beliveau BJ et al (2016) Spatial organization of chromatin domains and compartments in single chromosomes. Science 353, 598-602  https://doi.org/10.1126/science.aaf8084
  22. Dixon JR, Selvaraj S, Yue F et al (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376-380  https://doi.org/10.1038/nature11082
  23. Nora EP, Lajoie BR, Schulz EG et al (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381-385  https://doi.org/10.1038/nature11049
  24. Szabo Q, Bantignies F and Cavalli G (2019) Principles of genome folding into topologically associating domains. Sci Adv 5, eaaw1668 
  25. Fudenberg G, Imakaev M, Lu C, Goloborodko A, Abdennur N and Mirny LA (2016) Formation of chromosomal domains by loop extrusion. Cell Rep 15, 2038-2049  https://doi.org/10.1016/j.celrep.2016.04.085
  26. Naumova N, Imakaev M, Fudenberg G et al (2013) Organization of the mitotic chromosome. Science 342, 948-953  https://doi.org/10.1126/science.1236083
  27. Alipour E and Marko JF (2012) Self-organization of domain structures by DNA-loop-extruding enzymes. Nucleic Acids Res 40, 11202-11212  https://doi.org/10.1093/nar/gks925
  28. Schoenfelder S and Fraser P (2019) Long-range enhancer-promoter contacts in gene expression control. Nat Rev Genet 20, 437-455  https://doi.org/10.1038/s41576-019-0128-0
  29. Nora EP, Goloborodko A, Valton AL et al (2017) Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell 169, 930-944 e922 
  30. Nuebler J, Fudenberg G, Imakaev M, Abdennur N and Mirny LA (2018) Chromatin organization by an interplay of loop extrusion and compartmental segregation. Proc Natl Acad Sci U S A 115, E6697-E6706  https://doi.org/10.1073/pnas.1717730115
  31. Rao SSP, Huang SC, Glenn St Hilaire B et al (2017) Cohesin loss eliminates all loop domains. Cell 171, 305-320 e324 
  32. Schwarzer W, Abdennur N, Goloborodko A et al (2017) Two independent modes of chromatin organization revealed by cohesin removal. Nature 551, 51-56  https://doi.org/10.1038/nature24281
  33. Wutz G, Varnai C, Nagasaka K et al (2017) Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. EMBO J 36, 3573-3599  https://doi.org/10.15252/embj.201798004
  34. Spracklin G, Abdennur N, Imakaev M et al (2023) Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers. Nat Struct & Mol Biol 30, 38-51  https://doi.org/10.1038/s41594-022-00892-7
  35. Nichols MH and Corces VG (2021) Principles of 3D compartmentalization of the human genome. Cell Rep 35, 109330 
  36. Fortin JP and Hansen KD (2015) Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data. Genome Biol 16, 180 
  37. Mourad R and Cuvier O (2015) Predicting the spatial organization of chromosomes using epigenetic data. Genome Biol 16, 182 
  38. Pancaldi V, Carrillo-de-Santa-Pau E, Javierre BM et al (2016) Integrating epigenomic data and 3D genomic structure with a new measure of chromatin assortativity. Genome Biol 17, 152 
  39. Tolsma TO and Hansen JC (2019) Post-translational modifications and chromatin dynamics. Essays Biochem 63, 89-96  https://doi.org/10.1042/EBC20180067
  40. Tan ZW, Guarnera E and Berezovsky IN (2019) Exploring chromatin hierarchical organization via Markov State Modelling. PLoS Comput Biol 14, e1006686 
  41. Boettiger AN, Bintu B, Moffitt JR et al (2016) Superresolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529, 418-422  https://doi.org/10.1038/nature16496
  42. Kimura A and Horikoshi M (2004) Partition of distinct chromosomal regions: negotiable border and fixed border. Genes Cells 9, 499-508  https://doi.org/10.1111/j.1356-9597.2004.00740.x
  43. Wang J, Lawry ST, Cohen AL and Jia S (2014) Chromosome boundary elements and regulation of heterochromatin spreading. Cell Mol Life Sci 71, 4841-4852  https://doi.org/10.1007/s00018-014-1725-x
  44. Rao SS, Huntley MH, Durand NC 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
  45. Gassler J, Brandao HB, Imakaev M et al (2017) A mechanism of cohesin-dependent loop extrusion organizes zygotic genome architecture. EMBO J 36, 3600-3618  https://doi.org/10.15252/embj.201798083
  46. Nagano T, Lubling Y, Stevens TJ et al (2013) Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature 502, 59-64  https://doi.org/10.1038/nature12593
  47. Bintu B, Mateo LJ, Su JH et al (2018) Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells. Science 362, 1783-1791  https://doi.org/10.1126/science.aau1783
  48. Mateo LJ, Murphy SE, Hafner A, Cinquini IS, Walker CA and Boettiger AN (2019) Visualizing DNA folding and RNA in embryos at single-cell resolution. Nature 568, 49-54  https://doi.org/10.1038/s41586-019-1035-4
  49. Liu M, Lu Y, Yang B et al (2020) Multiplexed imaging of nucleome architectures in single cells of mammalian tissue. Nat Commun 11, 2907 
  50. Montavon T, Shukeir N, Erikson G et al (2021) Complete loss of H3K9 methylation dissolves mouse heterochromatin organization. Nat Commun 12, 4359 
  51. Yan Z, Ji L, Huo X et al (2020) G9a/GLP-sensitivity of H3K9me2 demarcates two types of genomic compartments. Genomics Proteomics Bioinformatics 18, 359-370  https://doi.org/10.1016/j.gpb.2020.08.001
  52. Feng Y, Wang Y, Wang X et al (2020) Simultaneous epigenetic perturbation and genome imaging reveal distinct roles of H3K9me3 in chromatin architecture and transcription. Genome Biol 21, 296 
  53. Buitrago D, Labrador M, Arcon JP et al (2021) Impact of DNA methylation on 3D genome structure. Nat Commun 12, 3243 
  54. McLaughlin K, Flyamer IM, Thomson JP et al (2019) DNA Methylation directs polycomb-dependent 3D genome re-organization in naive pluripotency. Cell Rep 29, 1974-1985 e1976 
  55. Wang H, Han M and Qi LS (2021) Engineering 3D genome organization. Nat Rev Genet 22, 343-360  https://doi.org/10.1038/s41576-020-00325-5
  56. Morgan SL, Mariano NC, Bermudez A et al (2017) Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping. Nat Commun 8, 15993 
  57. Hao N, Shearwin KE and Dodd IB (2017) Programmable DNA looping using engineered bivalent dCas9 complexes. Nat Commun 8, 1628 
  58. Deng W, Lee J, Wang H et al (2012) Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell 149, 1233-1244  https://doi.org/10.1016/j.cell.2012.03.051
  59. Kim JH, Rege M, Valeri J et al (2019) LADL: light-activated dynamic looping for endogenous gene expression control. Nat Methods 16, 633-639  https://doi.org/10.1038/s41592-019-0436-5
  60. Wang H, Xu X, Nguyen CM et al (2018) CRISPR-mediated programmable 3D genome positioning and nuclear organization. Cell 175, 1405-1417 e1414 
  61. Lin JL, Ekas H, Deaner M and Alper HS (2019) CRISPR-PIN: modifying gene position in the nucleus via dCas9- mediated tethering. Syn and Sys Biotech 4, 73-78  https://doi.org/10.1016/j.synbio.2019.02.001
  62. Grewal SI and Moazed D (2003) Heterochromatin and epigenetic control of gene expression. Science 301, 798-802  https://doi.org/10.1126/science.1086887
  63. Grewal SI and Elgin SC (2007) Transcription and RNA interference in the formation of heterochromatin. Nature 447, 399-406  https://doi.org/10.1038/nature05914
  64. Hojfeldt JW, Hedehus L, Laugesen A et al (2019) Noncore subunits of the PRC2 complex are collectively required for its target-site specificity. Mol Cell 76, 423-436 e423 
  65. Oksuz O, Narendra V, Lee CH et al (2018) Capturing the onset of PRC2-mediated repressive domain formation. Mol Cell 70, 1149-1162 e1145 
  66. Long Y, Hwang T, Gooding AR et al (2020) RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells. Nat Genet 52, 931-938  https://doi.org/10.1038/s41588-020-0662-x
  67. Yu JR, Lee CH, Oksuz O, Stafford JM and Reinberg D (2019) PRC2 is high maintenance. Genes Dev 33, 903-935  https://doi.org/10.1101/gad.325050.119
  68. Blackledge NP, Rose NR and Klose RJ (2015) Targeting polycomb systems to regulate gene expression: modifications to a complex story. Nat Rev Mol Cell Biol 16, 643-649  https://doi.org/10.1038/nrm4067
  69. Brickner JH (2023) Inheritance of epigenetic transcriptional memory through read-write replication of a histone modification. Ann N Y Acad Sci 1526, 50-58  https://doi.org/10.1111/nyas.15033
  70. Kikuchi M, Morita S, Wakamori M et al (2023) Epigenetic mechanisms to propagate histone acetylation by p300/CBP. Nat Commun 14, 4103 
  71. Serra-Cardona A, Duan S, Yu C and Zhang Z (2022) H3K4me3 recognition by the COMPASS complex facilitates the restoration of this histone mark following DNA replication. Science Adv 8, eabm6246 
  72. Kraft K, Yost KE, Murphy SE et al (2022) Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation. Proc Natl Acad Sci U S A 119, e2201883119 
  73. Lovkvist C, Mikulski P, Reeck S, Hartley M, Dean C and Howard M (2021) Hybrid protein assembly-histone modification mechanism for PRC2-based epigenetic switching and memory. Elife 10, e66454 
  74. Park M, Patel N, Keung AJ and Khalil AS (2019) Engineering epigenetic regulation using synthetic read-write modules. Cell 176, 227-238 e220 
  75. Sadaie M, Iida T, Urano T and Nakayama J (2004) A chromodomain protein, Chp1, is required for the establishment of heterochromatin in fission yeast. EMBO J 23, 3825-3835  https://doi.org/10.1038/sj.emboj.7600401
  76. Zhang K, Mosch K, Fischle W and Grewal SIS (2008) Roles of the Clr4 methyltransferase complex in nucleation, spreading and maintenance of heterochromatin. Nat Struct Mol Biol 15, 381-388  https://doi.org/10.1038/nsmb.1406
  77. Margueron R, Justin N, Ohno K et al (2009) Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461, 762-767  https://doi.org/10.1038/nature08398
  78. Lee SH, Li Y, Kim H et al (2022) The role of EZH1 and EZH2 in development and cancer. BMB Rep 55, 595-601  https://doi.org/10.5483/BMBRep.2022.55.12.174
  79. Lee CH, Yu JR, Kumar S et al (2018) Allosteric activation dictates PRC2 activity independent of its recruitment to chromatin. Mol Cell 70, 422-434 e426 
  80. Kilic S, Bachmann AL, Bryan LC and Fierz B (2015) Multivalency governs HP1α association dynamics with the silent chromatin state. Nat Commun 6, 7313 
  81. Larson AG, Elnatan D, Keenen MM et al (2017) Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547, 236-240  https://doi.org/10.1038/nature22822
  82. Strom AR, Emelyanov AV, Mir M, Fyodorov DV, Darzacq X and Karpen GH (2017) Phase separation drives heterochromatin domain formation. Nature 547, 241-245  https://doi.org/10.1038/nature22989
  83. Grewal SIS (2023) The molecular basis of heterochromatin assembly and epigenetic inheritance. Mol Cell 83, 1767-1785  https://doi.org/10.1016/j.molcel.2023.04.020
  84. Wang L, Gao Y, Zheng X et al (2019) Histone Modifications regulate chromatin compartmentalization by contributing to a phase separation mechanism. Mol Cell 76, 646-659 e646 
  85. Gao Y, Han M, Shang S, Wang H and Qi LS (2021) Interrogation of the dynamic properties of higher-order heterochromatin using CRISPR-dCas9. Mol Cell 81, 4287-4299 e4285 
  86. Ngan CY, Wong CH, Tjong H et al (2020) Chromatin interaction analyses elucidate the roles of PRC2-bound silencers in mouse development. Nat Genet 52, 264-272  https://doi.org/10.1038/s41588-020-0581-x
  87. Tiwari VK, McGarvey KM, Licchesi JDF et al (2008) PcG proteins, DNA methylation, and gene repression by chromatin looping. PLoS Biology 6, e306 
  88. Falk M, Feodorova Y, Naumova N et al (2019) Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature 570, 395-399  https://doi.org/10.1038/s41586-019-1275-3
  89. Mirny LA (2011) The fractal globule as a model of chromatin architecture in the cell. Chromosome Res 19, 37-51  https://doi.org/10.1007/s10577-010-9177-0
  90. Haddad N, Jost D and Vaillant C (2017) Perspectives: using polymer modeling to understand the formation and function of nuclear compartments. Chromosome Res 25, 35-50  https://doi.org/10.1007/s10577-016-9548-2
  91. MacPherson Q, Beltran B and Spakowitz AJ (2018) Bottom-up modeling of chromatin segregation due to epigenetic modifications. Proc Natl Acad Sci U S A 115, 12739-12744  https://doi.org/10.1073/pnas.1812268115
  92. Dodd IB, Micheelsen MA, Sneppen K and Thon G (2007) Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell 129, 813-822  https://doi.org/10.1016/j.cell.2007.02.053
  93. Erdel F and Greene EC (2016) Generalized nucleation and looping model for epigenetic memory of histone modifications. Proc Natl Acad Sci U S A 113, E4180-E4189  https://doi.org/10.1073/pnas.1605862113
  94. Michieletto D, Orlandini E and Marenduzzo D (2016) Polymer model with epigenetic recoloring reveals a pathway for the de novo establishment and 3D organization of chromatin domains. Physical Review X 6, 041047 
  95. Jeremy AO, Dino O and Leonid AM (2022) Design principles of 3D epigenetic memory systems. bioRxiv, 2022.2009.2024.509332 
  96. Cheng TH and Gartenberg MR (2000) Yeast heterochromatin is a dynamic structure that requires silencers continuously. Genes Dev 14, 452-463  https://doi.org/10.1101/gad.14.4.452
  97. Ragunathan K, Jih G and Moazed D (2015) Epigenetics. Epigenetic inheritance uncoupled from sequence-specific recruitment. Science 348, 1258699 
  98. Laprell F, Finkl K and Muller J (2017) Propagation of Polycomb-repressed chromatin requires sequence-specific recruitment to DNA. Science 356, 85-88  https://doi.org/10.1126/science.aai8266
  99. Abdulla AZ, Salari H, Tortora MMC, Vaillant C and Jost D (2023) 4D epigenomics: deciphering the coupling between genome folding and epigenomic regulation with biophysical modeling. Curr Opin Genet Dev 79, 102033 
  100. Abdulla AZ, Vaillant C and Jost D (2022) Painters in chromatin: a unified quantitative framework to systematically characterize epigenome regulation and memory. Nucleic Acids Res 50, 9083-9104  https://doi.org/10.1093/nar/gkac702
  101. Wells JN and Feschotte C (2020) A field guide to eukaryotic transposable elements. Annu Rev Genet 54, 539-561  https://doi.org/10.1146/annurev-genet-040620-022145
  102. Rebollo R, Karimi MM, Bilenky M et al (2011) Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms. PLoS Genet 7, e1002301 
  103. Newar K, Abdulla AZ, Salari H, Fanchon E and Jost D (2022) Dynamical modeling of the H3K27 epigenetic landscape in mouse embryonic stem cells. PLoS Comput Biol 18, e1010450 
  104. Imakaev MV, Fudenberg G and Mirny LA (2015) Modeling chromosomes: beyond pretty pictures. FEBS Lett 589, 3031-3036  https://doi.org/10.1016/j.febslet.2015.09.004
  105. Bau D and Marti-Renom MA (2012) Genome structure determination via 3C-based data integration by the Integrative Modeling Platform. Methods (San Diego, Calif.) 58, 300-306  https://doi.org/10.1016/j.ymeth.2012.04.004
  106. Marti-Renom MA and Mirny LA (2011) Bridging the resolution gap in structural modeling of 3D genome organization. PLoS Comput Biol 7, e1002125 
  107. Tjong H, Li W, Kalhor R et al (2016) Population-based 3D genome structure analysis reveals driving forces in spatial genome organization. Proc Natl Acad Sci U S A 113, E1663-E1672  https://doi.org/10.1073/pnas.1512577113
  108. Shukron O and Holcman D (2017) Transient chromatin properties revealed by polymer models and stochastic simulations constructed from chromosomal capture data. PLoS Comput Biol 13, e1005469 
  109. Dodero-Rojas E, Mello MF, Brahmachari S, Oliveira Junior AB, Contessoto VG and Onuchic JN (2023) PyMEGABASE: predicting cell-type-specific structural annotations of chromosomes using the epigenome. J Mol Biol 435, 168180 
  110. Xiong K and Ma J (2019) Revealing Hi-C subcompartments by imputing inter-chromosomal chromatin interactions. Nat Commun 10, 5069 
  111. Qi Y and Zhang B (2019) Predicting three-dimensional genome organization with chromatin states. PLoS Comput Biol 15, e1007024 
  112. Di Pierro M, Cheng RR, Lieberman Aiden E, Wolynes PG and Onuchic JN (2017) De novo prediction of human chromosome structures: epigenetic marking patterns encode genome architecture. Proc Natl Acad Sci U S A 114, 12126-12131  https://doi.org/10.1073/pnas.1714980114
  113. Ashoor H, Chen X, Rosikiewicz W et al (2020) Graph embedding and unsupervised learning predict genomic sub-compartments from HiC chromatin interaction data. Nat Commun 11, 1173 
  114. Zheng S, Thakkar N, Harris HL et al (2022) Predicting A/B compartments from histone modifications using deep learning. bioRxiv, 2022.2004.2019.488754  2022.2004.2019.488754
  115. Luo Y, Hitz BC, Gabdank I et al (2020) New developments on the Encyclopedia of DNA Elements (ENCODE) data portal. Nucleic Acids Res 48, D882-d889  https://doi.org/10.1093/nar/gkz1062
  116. Di Pierro M, Zhang B, Aiden EL, Wolynes PG and Onuchic JN (2016) Transferable model for chromosome architecture. Proc Natl Acad Sci U S A 113, 12168-12173  https://doi.org/10.1073/pnas.1613607113
  117. Contessoto VG, Cheng RR and Onuchic JN (2022) Uncovering the statistical physics of 3D chromosomal organization using data-driven modeling. Curr Opin Struct Biol 75, 102418