Abstract
How cells adopt different identities has long fascinated biologists. Signal transduction in response to environmental cues results in the activation of transcription factors that determine the gene-expression program characteristic of each cell type. Technological advances in the study of 3D chromatin folding are bringing the role of genome conformation in transcriptional regulation to the fore. Characterizing this role of genome architecture has profound implications, not only for differentiation and development but also for diseases including developmental malformations and cancer. Here we review recent studies indicating that the interplay between transcription and genome conformation is a driving force for cell-fate decisions.
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References
Davidson, E. H. Emerging properties of animal gene regulatory networks. Nature 468, 911–920 (2010).
Vaquerizas, J. M., Kummerfeld, S. K., Teichmann, S. A. & Luscombe, N. M. A census of human transcription factors: function, expression and evolution. Nat. Rev. Genet. 10, 252–263 (2009).
Lambert, S. A. et al. The human transcription factors. Cell 172, 650–665 (2018).
Kundaje, A. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–330 (2015).
de Laat, W. & Duboule, D. Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502, 499–506 (2013).
Zaret, K. S. & Mango, S. E. Pioneer transcription factors, chromatin dynamics, and cell fate control. Curr. Opin. Genet. Dev. 37, 76–81 (2016).
Spitz, F. & Furlong, E. E. Transcription factors: from enhancer binding to developmental control. Nat. Rev. Genet. 13, 613–626 (2012).
Voss, T. C. & Hager, G. L. Dynamic regulation of transcriptional states by chromatin and transcription factors. Nat. Rev. Genet. 15, 69–81 (2014).
Dekker, J. & Mirny, L. The 3D genome as moderator of chromosomal communication. Cell 164, 1110–1121 (2016).
Bonev, B. & Cavalli, G. Organization and function of the 3D genome. Nat. Rev. Genet. 17, 661–678 (2016).
Furlong, E. E. M. & Levine, M. Developmental enhancers and chromosome topology. Science 361, 1341–1345 (2018).
Novikoff, A. B. The concept of integrative levels and biology. Science 101, 209–215 (1945).
Graf, T. & Enver, T. Forcing cells to change lineages. Nature 462, 587–594 (2009).
Denker, A. & de Laat, W. The second decade of 3C technologies: detailed insights into nuclear organization. Genes Dev. 30, 1357–1382 (2016).
Yadav, T., Quivy, J. P. & Almouzni, G. Chromatin plasticity: a versatile landscape that underlies cell fate and identity. Science 361, 1332–1336 (2018).
Cremer, T. & Cremer, C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat. Rev. Genet. 2, 292–301 (2001).
Bronshtein, I. et al. Exploring chromatin organization mechanisms through its dynamic properties. Nucleus 7, 27–33 (2016).
Branco, M. R. & Pombo, A. Intermingling of chromosome territories in interphase suggests role in translocations and transcription-dependent associations. PLoS Biol. 4, e138 (2006).
Quinodoz, S. A. et al. Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus Cell 174, 744–757 (2018).
Spilianakis, C. G., Lalioti, M. D., Town, T., Lee, G. R. & Flavell, R. A. Interchromosomal associations between alternatively expressed loci. Nature 435, 637–645 (2005).
Lomvardas, S. et al. Interchromosomal interactions and olfactory receptor choice. Cell 126, 403–413 (2006).
Apostolou, E. & Thanos, D. Virus infection induces NF-κB-dependent interchromosomal associations mediating monoallelic IFNβ gene expression. Cell 134, 85–96 (2008).
Monahan, K., Horta, A. & Lomvardas, S. LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice. Nature 565, 448–453 (2019).
Schoenfelder, S. et al. Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells. Nat. Genet. 42, 53–61 (2010).
Yusufzai, T. M., Tagami, H., Nakatani, Y. & Felsenfeld, G. CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol. Cell 13, 291–298 (2004).
Brown, K. E. et al. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell 91, 845–854 (1997).
Lieberman-Aiden, E. et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289–293 (2009). A landmark paper reporting the development of the widely used Hi-C technology and describing the division of the human genome into two topological compartments, A and B.
Wijchers, P. J. et al. Characterization and dynamics of pericentromere-associated domains in mice. Genome Res. 25, 958–969 (2015).
Vieux-Rochas, M., Fabre, P. J., Leleu, M., Duboule, D. & Noordermeer, D. Clustering of mammalian Hox genes with other H3K27me3 targets within an active nuclear domain. Proc. Natl Acad. Sci. USA 112, 4672–4677 (2015).
van Steensel, B. & Belmont, A. S. Lamina-associated domains: links with chromosome architecture, heterochromatin, and gene repression. Cell 169, 780–791 (2017).
Therizols, P. et al. Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells. Science 346, 1238–1242 (2014).
Wijchers, P. J. et al. Cause and consequence of tethering a subTAD to different nuclear compartments. Mol. Cell 61, 461–473 (2016).
Harr, J. C. et al. Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins. J. Cell Biol. 208, 33–52 (2015).
Stadhouders, R. et al. Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming. Nat. Genet. 50, 238–249 (2018). The first study to describe the dynamics of mammalian genome conformation as somatic cells reprogram into pluripotent cells, during which a substantial number of loci, including those of key pluripotency factors, undergo topological changes in advance of transcriptional changes.
Maeshima, K., Ide, S., Hibino, K. & Sasai, M. Liquid-like behavior of chromatin. Curr. Opin. Genet. Dev. 37, 36–45 (2016).
Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K. & Sharp, P. A. A phase separation model for transcriptional control. Cell 169, 13–23 (2017).
Hyman, A. A., Weber, C. A. & Jülicher, F. Liquid–liquid phase separation in biology. Annu. Rev. Cell Dev. Biol. 30, 39–58 (2014).
Shin, Y. et al. Liquid nuclear condensates mechanically sense and restructure the genome Cell 175, 1481–1491 (2018).
Boija, A. et al. Transcription factors activate genes through the phase-separation capacity of their activation domains. Cell 175, 1842–1855 (2018).
Chong, S. et al. Imaging dynamic and selective low-complexity domain interactions that control gene transcription. Science 361, eaar2555 (2018). Together with ref. 39, this paper implicates transcription factors as direct mediators of phase separation.
de Wit, E. et al. The pluripotent genome in three dimensions is shaped around pluripotency factors. Nature 501, 227–231 (2013).
Liu, Z. et al. 3D imaging of Sox2 enhancer clusters in embryonic stem cells. eLife 3, e04236 (2014).
Bantignies, F. et al. Polycomb-dependent regulatory contacts between distant Hox loci in Drosophila. Cell 144, 214–226 (2011).
Boehning, M. et al. RNA polymerase II clustering through carboxy-terminal domain phase separation. Nat. Struct. Mol. Biol. 25, 833–840 (2018).
Lu, H. et al. Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature 558, 318–323 (2018).
Cho, W. K. et al. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science 361, 412–415 (2018).
Sabari, B. R. et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science 361, eaar3958 (2018).
Schoenfelder, S. et al. Polycomb repressive complex PRC1 spatially constrains the mouse embryonic stem cell genome. Nat. Genet. 47, 1179–1186 (2015).
Larson, A. G. et al. Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin. Nature 547, 236–240 (2017).
Strom, A. R. et al. Phase separation drives heterochromatin domain formation. Nature 547, 241–245 (2017).
Nora, E. P. et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485, 381–385 (2012).
Dixon, J. R. et al. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485, 376–380 (2012).
Sexton, T. et al. Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148, 458–472 (2012). Together with refs. 51,52, this study reports the existence of topologically associating domains as a principle of 3D genome organization.
Rao, S. S. et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680 (2014). An improved Hi-C protocol for high-resolution analysis that allows identification of chromatin loops and further refines A–B compartment segmentation.
Vietri Rudan, M. et al. Comparative Hi-C reveals that CTCF underlies evolution of chromosomal domain architecture. Cell Reports 10, 1297–1309 (2015).
Fudenberg, G. et al. Formation of chromosomal domains by loop extrusion. Cell Reports 15, 2038–2049 (2016).
Sanborn, A. L. et al. Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc. Natl Acad. Sci. USA 112, E6456–E6465 (2015).
Alipour, E. & Marko, J. F. Self-organization of domain structures by DNA-loop-extruding enzymes. Nucleic Acids Res. 40, 11202–11212 (2012).
Nuebler, J., Fudenberg, G., Imakaev, M., Abdennur, N. & Mirny, L. A. Chromatin organization by an interplay of loop extrusion and compartmental segregation. Proc. Natl Acad. Sci. USA 115, E6697–E6706 (2018).
Ulianov, S. V. et al. Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains. Genome Res. 26, 70–84 (2016).
Rowley, M. J. et al. Evolutionarily conserved principles predict 3D chromatin organization Mol. Cell 67, 837–852 (2017).
Rada-Iglesias, A., Grosveld, F. G. & Papantonis, A. Forces driving the three-dimensional folding of eukaryotic genomes. Mol. Syst. Biol. 14, e8214 (2018).
Nora, E. P. et al. Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization Cell 169, 930–944 (2017).Degron-mediated CTCF depletion in embryonic stem cells is used to show that the factor is essential for creating and maintaining TAD borders but not A–B compartments.
Wutz, G. et al. Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins. EMBO J. 36, 3573–3599 (2017).
Bonev, B. et al. Multiscale 3D genome rewiring during mouse neural development. Cell 171, 557–572 (2017).
Wei, Z. et al. Klf4 organizes long-range chromosomal interactions with the Oct4 locus in reprogramming and pluripotency. Cell Stem Cell 13, 36–47 (2013).
Abboud, N. et al. A cohesin–OCT4 complex mediates Sox enhancers to prime an early embryonic lineage. Nat. Commun. 6, 6749 (2015).
Hug, C. B., Grimaldi, A. G., Kruse, K. & Vaquerizas, J. M. Chromatin architecture emerges during zygotic genome activation independent of transcription. Cell 169, 216–228 (2017).
Brackley, C. A., Johnson, J., Kelly, S., Cook, P. R. & Marenduzzo, D. Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains. Nucleic Acids Res. 44, 3503–3512 (2016).
Phillips-Cremins, J. E. et al. Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153, 1281–1295 (2013).
Shen, Y. et al. A map of the cis-regulatory sequences in the mouse genome. Nature 488, 116–120 (2012).
Dowen, J. M. et al. Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell 159, 374–387 (2014).
Schoenfelder, S. et al. The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements. Genome Res. 25, 582–597 (2015).
Sun, F. et al. Promoter–enhancer communication occurs primarily within insulated neighborhoods. Mol. Cell 73, 250–263 (2019).
Lupiáñez, D. G. et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161, 1012–1025 (2015).The first study that convincingly links disruption of TAD structure to transcriptional deregulation as well as mouse and human limb malformations.
Flavahan, W. A. et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature 529, 110–114 (2016).
Hnisz, D. et al. Activation of proto-oncogenes by disruption of chromosome neighborhoods. Science 351, 1454–1458 (2016).
Dixon, J. R. et al. Chromatin architecture reorganization during stem cell differentiation. Nature 518, 331–336 (2015).
Le Dily, F. et al. Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation. Genes Dev. 28, 2151–2162 (2014).
Kagey, M. H. et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature 467, 430–435 (2010).
Andrey, G. & Mundlos, S. The three-dimensional genome: regulating gene expression during pluripotency and development. Development 144, 3646–3658 (2017).
Deng, W. et al. Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell 149, 1233–1244 (2012). The first conclusive evidence that forcing enhancer–promoter interactions is sufficient to alter gene expression.
Weintraub, A. S. et al. YY1 is a structural regulator of enhancer–promoter loops. Cell 171, 1573–1588 (2017).
Liu, Z. & Tjian, R. Visualizing transcription factor dynamics in living cells. J. Cell Biol. 217, 1181–1191 (2018).
Papantonis, A. & Cook, P. R. Transcription factories: genome organization and gene regulation. Chem. Rev. 113, 8683–8705 (2013).
Gu, B. et al. Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory elements. Science 359, 1050–1055 (2018).
Fraser, J., Williamson, I., Bickmore, W. A. & Dostie, J. An overview of genome organization and how we got there: from FISH to Hi-C. Microbiol. Mol. Biol. Rev. 79, 347–372 (2015).
Peric-Hupkes, D. et al. Molecular maps of the reorganization of genome-nuclear lamina interactions during differentiation. Mol. Cell 38, 603–613 (2010).
Hu, G. et al. Transformation of accessible chromatin and 3D nucleome underlies lineage commitment of early T cells. Immunity 48, 227–242 (2018).
Krijger, P. H. et al. Cell-of-origin-specific 3D genome structure acquired during somatic cell reprogramming. Cell Stem Cell 18, 597–610 (2016).
Pekowska, A. et al. Gain of CTCF-anchored chromatin loops marks the exit from naive pluripotency. Cell Syst. 7, 482–495 (2018).
Kieffer-Kwon, K. R. et al. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell 155, 1507–1520 (2013).
Javierre, B. M. et al. Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters. Cell 167, 1369–1384 (2016).
Zhang, Y. et al. Chromatin connectivity maps reveal dynamic promoter–enhancer long-range associations. Nature 504, 306–310 (2013).
Tan, L., Xing, D., Chang, C. H., Li, H. & Xie, X. S. Three-dimensional genome structures of single diploid human cells. Science 361, 924–928 (2018).
Ulianov, S. V., Tachibana-Konwalski, K. & Razin, S. V. Single-cell Hi-C bridges microscopy and genome-wide sequencing approaches to study 3D chromatin organization. BioEssays 39, 1700104 (2017).
Stevens, T. J. et al. 3D structures of individual mammalian genomes studied by single-cell Hi-C. Nature 544, 59–64 (2017).
Flyamer, I. M. et al. Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition. Nature 544, 110–114 (2017).
Bintu, B. et al. Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells. Science 362, eaau1783 (2018). Super-resolution imaging is used to show that TADs exist in single cells with variable boundaries, and cohesin is shown to specifically control preferential boundary positioning.
Hansen, A. S., Cattoglio, C., Darzacq, X. & Tjian, R. Recent evidence that TADs and chromatin loops are dynamic structures. Nucleus 9, 20–32 (2018).
Rao, S. S. P. et al. Cohesin loss eliminates all loop domains. Cell 171, 305–320 (2017).
Johanson, T. M. et al. Transcription-factor-mediated supervision of global genome architecture maintains B cell identity. Nat. Immunol. 19, 1257–1264 (2018).
Chen, H. et al. Dynamic interplay between enhancer-promoter topology and gene activity. Nat. Genet. 50, 1296–1303 (2018).
Andrey, G. et al. A switch between topological domains underlies HoxD genes collinearity in mouse limbs. Science 340, 1234167 (2013).
Symmons, O. et al. Functional and topological characteristics of mammalian regulatory domains. Genome Res. 24, 390–400 (2014).
Liu, H. et al. Visualizing long-term single-molecule dynamics in vivo by stochastic protein labeling. Proc. Natl Acad. Sci. USA 115, 343–348 (2018).
de Wit, E. et al. CTCF binding polarity determines chromatin looping. Mol. Cell 60, 676–684 (2015).
Guo, Y. et al. CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell 162, 900–910 (2015).
Narendra, V. et al. CTCF establishes discrete functional chromatin domains at the Hox clusters during differentiation. Science 347, 1017–1021 (2015).
Krijger, P. H. & de Laat, W. Regulation of disease-associated gene expression in the 3D genome. Nat. Rev. Mol. Cell Biol. 17, 771–782 (2016).
Sun, J. H. et al. Disease-associated short tandem repeats co-localize with chromatin domain boundaries. Cell 175, 224–238 (2018).
Schwarzer, W. et al. Two independent modes of chromatin organization revealed by cohesin removal. Nature 551, 51–56 (2017). In vivo depletion of the cohesin loading factor Nipbl leads to genome-wide loss of TAD organization, whereas A–B compartmentalization is strengthened, suggesting that TAD formation and compartmentalization are separate antagonistic processes.
Haarhuis, J. H. I. et al. The cohesin release factor WAPL restricts chromatin loop extension. Cell 169, 693–707 (2017). Dissection of the functional role of cohesin loading and release factors in chromatin loop formation and their size.
Beagrie, R. A. et al. Complex multi-enhancer contacts captured by genome architecture mapping. Nature 543, 519–524 (2017).
Cuartero, S. et al. Control of inducible gene expression links cohesin to hematopoietic progenitor self-renewal and differentiation. Nat. Immunol. 19, 932–941 (2018). Demonstration that the induction of inflammatory response genes in haematopoietic cells is highly dependent on cohesin.
Wang, S. et al. Spatial organization of chromatin domains and compartments in single chromosomes. Science 353, 598–602 (2016).
Krijger, P. H. & de Laat, W. Identical cells with different 3D genomes; cause and consequences? Curr. Opin. Genet. Dev. 23, 191–196 (2013).
Ghavi-Helm, Y. et al. Enhancer loops appear stable during development and are associated with paused polymerase. Nature 512, 96–100 (2014).
Jin, F. et al. A high-resolution map of the three-dimensional chromatin interactome in human cells. Nature 503, 290–294 (2013).
Li, L. et al. Widespread rearrangement of 3D chromatin organization underlies polycomb-mediated stress-induced silencing. Mol. Cell 58, 216–231 (2015).
Palstra, R. J. et al. Maintenance of long-range DNA interactions after inhibition of ongoing RNA polymerase II transcription. PLoS ONE 3, e1661 (2008).
Mitchell, J. A. & Fraser, P. Transcription factories are nuclear subcompartments that remain in the absence of transcription. Genes Dev. 22, 20–25 (2008).
Apostolou, E. et al. Genome-wide chromatin interactions of the Nanog locus in pluripotency, differentiation, and reprogramming. Cell Stem Cell 12, 699–712 (2013).
Oudelaar, A. M. et al. Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains. Nat. Genet. 50, 1744–1751 (2018).
Allahyar, A. et al. Enhancer hubs and loop collisions identified from single-allele topologies. Nat. Genet. 50, 1151–1160 (2018).
Denholtz, M. et al. Long-range chromatin contacts in embryonic stem cells reveal a role for pluripotency factors and polycomb proteins in genome organization. Cell Stem Cell 13, 602–616 (2013).
Corrales, M. et al. Clustering of Drosophila housekeeping promoters facilitates their expression. Genome Res. 27, 1153–1161 (2017).
Bernstein, B. E. et al. A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125, 315–326 (2006).
Stadhouders, R. et al. Control of developmentally primed erythroid genes by combinatorial co-repressor actions. Nat. Commun. 6, 8893 (2015).
Cruz-Molina, S. et al. PRC2 facilitates the regulatory topology required for poised enhancer function during pluripotent stem cell differentiation. Cell Stem Cell 20, 689–705 (2017).
Mas, G. et al. Promoter bivalency favors an open chromatin architecture in embryonic stem cells. Nat. Genet. 50, 1452–1462 (2018).
Zirkel, A. et al. HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types. Mol. Cell 70, 730–744 (2018).
Beagan, J. A. et al. Local genome topology can exhibit an incompletely rewired 3D-folding state during somatic cell reprogramming. Cell Stem Cell 18, 611–624 (2016).
Ribeiro de Almeida, C., Hendriks, R. W. & Stadhouders, R. Dynamic control of long-range genomic interactions at the immunoglobulin κ light-chain locus. Adv. Immunol. 128, 183–271 (2015).
Kosak, S. T. et al. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296, 158–162 (2002).
Jhunjhunwala, S. et al. The 3D structure of the immunoglobulin heavy-chain locus: implications for long-range genomic interactions. Cell 133, 265–279 (2008).
Fuxa, M. et al. Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene. Genes Dev. 18, 411–422 (2004).
Guo, C. et al. CTCF-binding elements mediate control of V(D)J recombination. Nature 477, 424–430 (2011).
Ribeiro de Almeida, C. et al. The DNA-binding protein CTCF limits proximal Vκ recombination and restricts κ enhancer interactions to the immunoglobulin κ light chain locus. Immunity 35, 501–513 (2011).
Stadhouders, R. et al. Pre-B cell receptor signaling induces immunoglobulin κ locus accessibility by functional redistribution of enhancer-mediated chromatin interactions. PLoS Biol. 12, e1001791 (2014). A report showing that signal-responsive transcription factors during B cell development can induce a functional redistribution of existing 3D enhancer–promoter interactions, a phenomenon called enhancer focusing.
Noordermeer, D. et al. Variegated gene expression caused by cell-specific long-range DNA interactions. Nat. Cell Biol. 13, 944–951 (2011).
Gröschel, S. et al. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia. Cell 157, 369–381 (2014). A study showing that disrupted TAD organization can have major consequences for cancer development: chromosomal abnormalities enable a GATA2 enhancer to ectopically activate the EVI1 oncogene while silencing GATA2, together resulting in cellular transformation.
Laurenti, E. & Göttgens, B. From haematopoietic stem cells to complex differentiation landscapes. Nature 553, 418–426 (2018).
Wang, H. et al. CRISPR-mediated programmable 3D genome positioning and nuclear organization. Cell 175, 1405–1417 (2018).
Barrington, C., Finn, R. & Hadjur, S. Cohesin biology meets the loop extrusion model. Chromosome Res. 25, 51–60 (2017).
Ke, Y. et al. Chromatin structures of mature gametes and structural reprogramming during mammalian embryogenesis Cell 170, 367–381 (2017).
Du, Z. et al. Allelic reprogramming of 3D chromatin architecture during early mammalian development. Nature 547, 232–235 (2017).
Gassler, J. et al. A mechanism of cohesin-dependent loop extrusion organizes zygotic genome architecture. EMBO J. 36, 3600–3618 (2017).
Jung, Y. H. et al. Chromatin states in mouse sperm correlate with embryonic and adult regulatory landscapes. Cell Reports 18, 1366–1382 (2017).
Kaaij, L. J. T., van der Weide, R. H., Ketting, R. F. & de Wit, E. Systemic loss and gain of chromatin architecture throughout zebrafish development. Cell Reports 24, 1–10 (2018).
Meshorer, E. et al. Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev. Cell 10, 105–116 (2006).
Acknowledgements
We apologize to the authors of many relevant studies for not citing their work owing to space limitations. We thank members of the Stadhouders, Filion and Graf laboratories for helpful discussions. G.F. and T.G. are supported by the European Research Council under the 7th Framework Programme FP7/2007-2013 (ERC Synergy Grant 4D-Genome, grant agreement 609989). R.S. is supported by the Netherlands Organization for Scientific Research (VENI 91617114) and an Erasmus MC Fellowship.
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R.S. and T.G. conceived and wrote the manuscript with essential input from G.J.F. Figures were prepared by R.S.
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Stadhouders, R., Filion, G.J. & Graf, T. Transcription factors and 3D genome conformation in cell-fate decisions. Nature 569, 345–354 (2019). https://doi.org/10.1038/s41586-019-1182-7
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DOI: https://doi.org/10.1038/s41586-019-1182-7
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