References
- Cramer P. Organization and regulation of gene transcription. Nature. 2019;224:1–15.
- Banani SF, Lee HO, Hyman AA, et al. Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Bio. 2017;18(5):285–298.
- Hirose T, Ninomiya K, Nakagawa S, et al. A guide to membraneless organelles and their various roles in gene regulation. Nat Rev Mol Cell Bio. 2022;24(4):1–17.
- Hyman AA, Weber CA, Jülicher F. Liquid-liquid phase separation in biology. Annu Rev Cell Dev Biol. 2014;30(1):39–58.
- Musacchio A. On the role of phase separation in the biogenesis of membraneless compartments. Embo J. 2022;41(5):e109952.
- McSwiggen DT, Mir M, Darzacq X, et al. Evaluating phase separation in live cells: diagnosis, caveats, and functional consequences. Genes & Dev. 2019;33(23–24):1619–1634. InternetAvailable from. http://genesdev.cshlp.org/content/early/2019/10/08/gad.331520.119.short?rss=1.
- Mittag T, Pappu RV. A conceptual framework for understanding phase separation and addressing open questions and challenges. Mol Cell. 2022;82(12):2201–2214.
- Hilbert L, Sato Y, Kuznetsova K, et al. Transcription organizes euchromatin via microphase separation. Nat Commun. 2021;12(1):1360. InternetAvailable from: https://ezproxy-prd.bodleian.ox.ac.uk:2268/articles/s41467-021-21589-3
- Feric M, Misteli T. Function moves biomolecular condensates in phase space. BioEssays. 2022;44(5):2200001.
- Cai D, Feliciano D, Dong P, et al. Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression. Nat Cell Biol. 2019;21(12):1578–1589. InternetAvailable from: https://www.nature.com/articles/s41556-019-0433-z
- Chowdhary S, Kainth AS, Paracha S, et al. Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response. Mol Cell. 2022;82(22):4386–4399.e7.
- Ahn JH, Davis ES, Daugird TA, et al. Phase separation drives aberrant chromatin looping and cancer development. Nature. 2021;595(7868):1–5. DOI:10.1038/s41586-021-03662-5
- Lyon AS, Peeples WB, Rosen MK. A framework for understanding the functions of biomolecular condensates across scales. Nat Rev Mol Cell Biol. 2020;18:1–21. InternetAvailable from. https://www.nature.com/articles/s41580-020-00303-z
- Cai D, Liu Z, Lippincott-Schwartz J. Biomolecular condensates and their links to cancer progression. Trends Biochem Sci. 2021;46(7):535–549.
- Elbaum-Garfinkle S. Matter over mind: liquid phase separation and neurodegeneration. J Biol Chem. 2019;294(18):7160–7168.
- Olins DE, Olins AL. Epichromatin and chromomeres: a ‘fuzzy’ perspective. Open Biol. 2018;8(6):180058. InternetAvailable from: https://royalsocietypublishing.org/doi/full/10.1098/rsob.180058.
- Cremer T, Cremer C, Baumann H, et al. Rabl’s model of the interphase chromosome arrangement tested in Chinese hamster cells by premature chromosome condensation and laser-UV-microbeam experiments. Hum Genet. 1982;60(1):46–56.
- Cremer T, Cremer C Chromosome territories, nuclear architecture and gene regulation in mammalian cells. 2001; Available from: http://www.nature.com/nrg/journal/v2/n4/abs/nrg0401_292a.html
- Cremer T, Cremer M, Hübner B, et al. The interchromatin compartment participates in the structural and functional organization of the cell nucleus. BioEssays: news and reviews in molecular, cellular and developmental biology. BioEssays. 2020;42(2):1900132. Internet. DOI:10.1002/bies.201900132.
- Jackson DA, Hassan AB, Errington RJ, et al. Visualization of focal sites of transcription within human nuclei. Embo J. 1993;12(3):1059–1065.
- Iborra FJ, Pombo A, Jackson DA, et al. Active RNA polymerases are localized within discrete transcription “factories’ in human nuclei. J Cell Sci. 1996;109(6):1427–1436.
- Cook PR. The organization of replication and transcription. Science. 1999;284(5421):1790–1795.
- Strickfaden H, Tolsma TO, Sharma A, et al. Condensed chromatin behaves like a solid on the mesoscale in vitro and in living cells. Cell. 2020;183(7):0. InternetAvailable from: https://www.cell.com/cell/fulltext/S0092-8674(20)31544-0#secsectitle0010.
- Gibson BA, Doolittle LK, Schneider MWG, et al. Organization of chromatin by intrinsic and regulated phase separation. Cell. 2019;179(2):470–484.e21. InternetAvailable from: https://www.sciencedirect.com/science/article/pii/S0092867419309560?via%3Dihub#undfig1
- Toretsky JA, Wright PE. Assemblages: functional units formed by cellular phase separation. J Cell Bio. 2014;206(5):579–588.
- Mora A, Huang X, Jauhari S, et al. Chromatin Hubs: a biological and computational outlook. Comput Struct Biotechnology J. 2022;20:3796–3813.
- Guo C, Luo Z, Lin C. Phase separation properties in transcriptional organization. Biochemistry-Us. 2022;61(22):2456–2460.
- Morin JA, Wittmann S, Choubey S, et al. Sequence-dependent surface condensation of a pioneer transcription factor on DNA. Nat Phys. 2022;18(3):1–6.
- Pancholi A, Klingberg T, Zhang W, et al. RNA polymerase II clusters form in line with liquid phase wetting of chromatin. bioRxiv. 2021;6:2021.02.03.429626. Internet.
- Hur W Jr, Tarzia JPK, Deneke M, et al. SD. CDK-Regulated phase separation seeded by histone genes ensures precise growth and function of histone locus bodies. Dev Cell. 2020;54(3):379–394.e6.
- Tchurikov NA, Kravatsky YV. The role of rDNA clusters in global epigenetic gene regulation. Frontiers Genetics. 2021;12:730633.
- Minezaki Y, Homma K, Kinjo AR, et al. Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation. J Mol Biol. 2006;359(4):1137–1149.
- Liu J, Perumal NB, Oldfield CJ, et al. Intrinsic disorder in transcription factors. Biochemistry-Us. 2006;45(22):6873–6888.
- Basu S, Mackowiak SD, Niskanen H, et al. Unblending of transcriptional condensates in human repeat expansion disease. Cell. 2020;181(5):1062–1079.e30. Internet. doi: 10.1016/j.cell.2020.04.018.
- Boija A, Klein IA, Sabari BR, et al. Transcription factors activate genes through the phase-separation capacity of their activation domains. Cell. 2018;175(7):1842–1855.e16. Internet. doi: 10.1016/j.cell.2018.10.042.
- Asimi V, Kumar AS, Niskanen H, et al. Hijacking of transcriptional condensates by endogenous retroviruses. Nat Genet. 2022;54(8):1238–1247.
- Hnisz D, Shrinivas K, Young RA, et al. A phase separation model for transcriptional control. Cell. 2017;169(1):13–23.
- Mir M, Stadler MR, Ortiz SA, et al. Dynamic multifactor hubs interact transiently with sites of active transcription in Drosophila embryos. Elife. 2018;7:8088. Available from. https://elifesciences.org/articles/40497
- Chong S, Graham TGW, Dugast-Darzacq C, et al. Tuning levels of low-complexity domain interactions to modulate endogenous oncogenic transcription. Mol Cell. 2022;82(11):2084–2097.e5.
- Liu Z, Tjian R. Visualizing transcription factor dynamics in living cells. J Cell Bio. 2018;10:jcb.201710038. InternetAvailable from: http://jcb.rupress.org/content/early/2018/01/26/jcb.201710038.
- Garcia DA, Johnson TA, Presman DM, et al. An intrinsically disordered region-mediated confinement state contributes to the dynamics and function of transcription factors. Mol Cell. 2021;81(7):1484–1498.e6. DOI:10.1016/j.molcel.2021.01.013
- Cho W-K, Spille J-H, Hecht M, et al. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science. 2018;361(6400):412–415.
- Boehning M, Dugast-Darzacq C, Rankovic M, et al. RNA polymerase II clustering through carboxy-terminal domain phase separation. Nat Struct Mol Biol. 2018;25(9):833–840. Internet. doi: 10.1038/s41594-018-0112-y.
- Lu H, Yu D, Hansen AS, et al. Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature. 2018;558(7709):318–323.
- Guo YE, Manteiga JC, Henninger JE, et al. Pol II phosphorylation regulates a switch between transcriptional and splicing condensates. Nature. 2019;572(7770):543–548. Internet. doi: 10.1038/s41586-019-1464-0.
- Chong S, Dugast-Darzacq C, Liu Z, et al. Imaging dynamic and selective low-complexity domain interactions that control gene transcription. Science. 2018;361(6400):361. DOI:10.1126/science.aar2555
- Chen Y, Cattoglio C, Dailey GM, et al. Mechanisms governing target search and binding dynamics of hypoxia-inducible factors. Elife. 2022;11:e75064.
- Wei M-T, Chang Y-C, Shimobayashi SF, et al. Nucleated transcriptional condensates amplify gene expression. Nat Cell Biol. 2020;324:1–10. InternetAvailable from. https://www.nature.com/articles/s41556-020-00578-6?code=22a258fb-cb32-4a7e-ac35-d36ce6ccf58f&error=cookies_not_supported
- Wang W, Qiao S, Li G, et al. A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated enhancer clusters. Nucleic Acids Res. 2022;50(9):4917–4937. DOI:10.1093/nar/gkac233
- Trojanowski J, Frank L, Rademacher A, et al. Transcription activation is enhanced by multivalent interactions independent of phase separation. Mol Cell. 2022;82(10):1878–1893.e10.
- Rawat P, Boehning M, Hummel B, et al. Stress-induced nuclear condensation of NELF drives transcriptional downregulation. Mol Cell. 2021;81(5):1013–1026.e11. DOI:10.1016/j.molcel.2021.01.016
- Wu J, Chen B, Liu Y, et al. Modulating gene regulation function by chemically controlled transcription factor clustering. Nat Commun. 2022;13(1):2663.
- Henninger JE, Oksuz O, Shrinivas K, et al. RNA-mediated feedback control of transcriptional condensates. Cell. 2020;184(1):207–225.e24. InternetAvailable from: https://www.sciencedirect.com/science/article/abs/pii/S0092867420315671
- Goronzy IN, Quinodoz SA, Jachowicz JW, et al. Simultaneous mapping of 3D structure and nascent RNAs argues against nuclear compartments that preclude transcription. Cell Rep. 2022;41(9):111730.
- Klosin A, Oltsch F, Harmon T, et al. Phase separation provides a mechanism to reduce noise in cells. Science. 2020;367(6476):464–468. InternetAvailable from: https://science.sciencemag.org/content/367/6476/464?utm_campaign=toc_sci-mag_2020-01-23&et_rid=35352841&et_cid=3176381
- Bhat P, Honson D, Guttman M. Nuclear compartmentalization as a mechanism of quantitative control of gene expression. Nat Rev Mol Cell Bio. 2021;22(10):1–18.
- Jensen TH, Jacquier A, Libri D. Dealing with pervasive transcription. Mol Cell. 2013;52(4):473–484.
- Franklin JM, Guan K-L. YAP/TAZ phase separation for transcription. Nat Cell Biol. 2020;22(4):357–358.
- Lu Y, Wu T, Gutman O, et al. Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression. Nat Cell Biol. 2020;19:491–512. InternetAvailable from. https://www.nature.com/articles/s41556-020-0485-0?code=59a25796-6bb6-475f-aa49-f00e185157be&error=cookies_not_supported
- Liu G, Dean A. Enhancer long-range contacts: the multi-adaptor protein LDB1 is the tie that binds. Biochim Biophys Acta, Gene Regul Mech. 2019;1862(6):625–633.
- Blobel GA, Higgs DR, Mitchell JA, et al. Testing the super-enhancer concept. Nat Rev Genet. 2021;22(12):1–7.
- Mir M, Bickmore W, Furlong EEM, et al. Chromatin topology, condensates and gene regulation: shifting paradigms or just a phase? Development. 2019;146(19):dev182766. InternetAvailable from: https://dev.biologists.org/content/146/19/dev182766
- Pachano T, Haro E, Rada-Iglesias A. Enhancer-gene specificity in development and disease. Development. 2022;149(11):149.
- Hsieh TH, Cattoglio C, Slobodyanyuk E, et al. Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1. Nat Genet. 2022;54(12):1919–1932.
- Chen Z, Snetkova V, Bower G, et al. Widespread Increase in Enhancer—Promoter Interactions during Developmental Enhancer Activation in Mammals. bioRxiv. 2022;2022.11.18.516017.
- Benabdallah NS, Williamson I, Illingworth RS, et al. Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation. Molecular Cell. 2019;0. InternetAvailable from. https://www.cell.com/molecular-cell/fulltext/S1097-27651930593-3
- Williamson I, Kane L, Devenney PS, et al. Developmentally regulated Shh expression is robust to TAD perturbations. Development. 2019;146:dev179523.
- Friman ET, Flyamer IM, Boyle S, et al. Ultra-long-range interactions between active regulatory elements. bioRxiv. 2022;2022.11.30.518557 DOI:10.1101/2022.11.30.518557.
- Hnisz D, Schuijers J, Lin CY, et al. Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers. molecular cell. 2015;58(2):362–370. InternetAvailable from: http://www.sciencedirect.com/science/article/pii/S1097276515001288
- Sabari BR, Dall’agnese A, Boija A, et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science. 2018;361(6400):361. DOI:10.1126/science.aar3958
- Shrinivas K, Sabari BR, Coffey EL, et al. Enhancer features that drive formation of transcriptional condensates. Molecular Cell. 2019;75(3):549–561.e7. InternetAvailable from: https://www.cell.com/molecular-cell/fulltext/S1097-27651930539-8?dgcid=raven_jbs_etoc_email
- Ramasamy S, Aljahani A, Karpinska MA, et al. The Mediator complex regulates enhancer-promoter interactions. bioRxiv. 2022;2022.06.15.496245.
- Zamudio AV, Dall’agnese A, Henninger JE, et al. Mediator condensates localize signaling factors to key cell identity genesMediates. Molecular Cell. 2019;76(5):753766.e6):753766.e6753–766.e6. DOI:10.1016/j.molcel.2019.08.016
- Gryder BE, Pomella S, Sayers C, et al. Histone hyperacetylation disrupts core gene regulatory architecture in rhabdomyosarcoma. Nature Genet. 2019;51(12):1714–1722. InternetAvailable from: https://www.nature.com/articles/s41588-019-0534-4
- Jia P, Li X, Wang X, et al. ZMYND8 mediated liquid condensates spatiotemporally decommission the latent super-enhancers during macrophage polarization. Nat Commun. 2021;12(1):6535. DOI:10.1038/s41467-021-26864-x
- Nair SJ, Yang L, Meluzzi D, et al. Phase separation of ligand-activated enhancers licenses cooperative chromosomal enhancer assembly. Nat Struct Mol Biol. 2019;26(3):193–203. InternetAvailable from: https://www.nature.com/articles/s41594-019-0190-5
- Shi B, Li W, Song Y, et al. UTX condensation underlies its tumour-suppressive activity. Nature. 2021;597(7878):1–6. DOI:10.1038/s41586-021-03903-7
- Schiessel H. Spatial and temporal organization of chromatin at small and large scales. Annu Rev Conden Ma P. 2022;14(1):14.
- Gelléri M, Chen S-Y, Szczurek A, et al. True-to-scale DNA-density maps correlate with major accessibility differences between active and inactive chromatin. bioRxiv. 2022;2022.03.23.485308.
- Smeets D, Markaki Y, Schmid VJ, et al. 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. 2014;7(1):8. DOI:10.1186/1756-8935-7-8
- Miron E, Oldenkamp R, Brown JM, et al. Chromatin arranges in chains of mesoscale domains with nanoscale functional topography independent of cohesin. Sci Adv. 2020;6(39):eaba8811. InternetAvailable from: https://advances.sciencemag.org/content/6/39/eaba8811
- Xu J, Ma H, Jin J, et al. Super-resolution imaging of higher-order chromatin structures at different epigenomic states in single mammalian cells. Cell Rep. 2018;24(4):873–882. InternetAvailable from: https://www.cell.com/cell-reports/fulltext/S2211-12471831012-X
- Gamliel A, Meluzzi D, Oh S, et al. Long-distance association of topological boundaries through nuclear condensates. Proc Natl Acad Sci. 2022;119(32):e2206216119.
- Banani SF, Afeyan LK, Hawken SW, et al. Genetic variation associated with condensate dysregulation in disease. Dev Cell. 2022;57(14):1776–1788.e8. DOI:10.1016/j.devcel.2022.06.010
- Oka M, Mura S, Otani M, et al. Chromatin-bound CRM1 recruits SET-Nup214 and NPM1c onto HOX clusters causing aberrant HOX expression in leukemia cells. Elife. 2019;8:1195. InternetAvailable from. https://elifesciences.org/articles/46667?utm_source=content_alert&utm_medium=email&utm_content=fulltext&utm_campaign=25-November-19-elife-alert
- Hao S, Fuehrer H, Flores E, et al. YAP condensates are highly organized hubs for YAP/TEAD transcription. bioRxiv. 2022;2022.10.24.513621.
- Yu M, Peng Z, Qin M, et al. Interferon-γ induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation. Mol Cell. 2021;81(6):1216–1230.e9. InternetAvailable from: https://www.cell.com/molecular-cell/fulltext/S1097-27652100010-1?dgcid=raven_jbs_etoc_email
- Frank F, Liu X, Ortlund EA. Glucocorticoid receptor condensates link DNA-dependent receptor dimerization and transcriptional transactivation. Proc Natl Acad Sci. 2021;118(30):e2024685118.
- Basu S, Martínez-Cristóbal P, Pesarrodona M, et al. Androgen receptor condensates as drug targets. bioRxiv. 2022;2022.08.18.504385.
- Klein IA, Boija A, Afeyan LK, et al. Partitioning of cancer therapeutics in nuclear condensates. Science. 2020;368(6497):1386–1392. InternetAvailable from: https://www.science.sciencemag.org/content/368/6497/1386.
- Zhang F, Wong S, Lee J, et al. Dynamic phase separation of the androgen receptor and its coactivators key to regulate gene expression. Nucleic Acids Research. 2023;51(1):99–116 https://doi.org/10.1093/nar/gkac1158.
- Xie J, He H, Kong W, et al. Targeting androgen receptor phase separation to overcome antiandrogen resistance. Nat Chem Biol. 2022;18(12):1–10. DOI:10.1038/s41589-022-01151-y
- Song L, Yao X, Li H, et al. Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer. Mol Cell. 2022;82(21):4080–4098.e12. DOI:10.1016/j.molcel.2022.09.034
- Hastings RL, Boeynaems S. Designer condensates: a toolkit for the biomolecular architect. J Mol Biol. 2021;433(12):166837.
- Mitrea DM, Mittasch M, Gomes BF, et al. Modulating biomolecular condensates: a novel approach to drug discovery. Nat Rev Drug Discov. 2022;21(11):1–22.
- Alberti S, Gladfelter A, Mittag T. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell. 2019;176(3):419–434. InternetAvailable from: https://www.cell.com/cell/fulltext/S0092-86741831649-0?dgcid=raven_jbs_etoc
- Irgen-Gioro S, Walling V, Chong S. Fixation can change the appearance of phase separation in living cells. eLife. 2022;(11):e79903.
- Gao Y, Li X, Li P, et al. A brief guideline for studies of phase-separated biomolecular condensates. Nat Chem Biol. 2022;18(12):1307–1318.
- Itoh Y, Iida S, Tamura S, et al. 1,6-hexanediol rapidly immobilizes and condenses chromatin in living human cells. Life Sci Alliance. 2021;4(4):e202001005. InternetAvailable from: https://www.life-science-alliance.org/content/4/4/e202001005
- Meduri R, Rubio LS, Mohajan S, et al. Phase-separation antagonists potently inhibit transcription and broadly increase nucleosome density. J Biol Chem. 2022;298(10):102365.
- Kempfer R, Pombo A. Methods for mapping 3D chromosome architecture. Nat Rev Genet. 2019;16:1–20. InternetAvailable from. https://www.nature.com/articles/s41576-019-0195-2
- Quinodoz SA, Bhat P, Chovanec P, et al. SPRITE: a genome-wide method for mapping higher-order 3D interactions in the nucleus using combinatorial split-and-pool barcoding. Nat Protoc. 2022;17(1):36–75.
- Quinodoz SA, Ollikainen N, Tabak B, et al. Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus. Cell. 2018;174(3):744–757.e24. InternetAvailable from: https://www.cell.com/cell/fulltext/S0092-86741830636-6?dgcid=raven_jbs_etoc_email
- Quinodoz SA, Bhat P, Ollikainen N, et al. RNA promotes the formation of spatial compartments in the nucleus. Cell. 2021;184(23):5775–5790.e30.
- Baggett DW, Medyukhina A, Tripathi S, et al. An image analysis pipeline for quantifying the features of fluorescently-labeled biomolecular condensates in cells. Frontiers Bioinform. 2022;2:897238.
- Ouyang W, Bai J, Singh MK, et al. ShareLoc — an open platform for sharing localization microscopy data. Nat Methods. 2022;19(11):1331–1333. DOI:10.1038/s41592-022-01659-0
- Muzzopappa F, Hummert J, Anfossi M, et al. Detecting and quantifying liquid–liquid phase separation in living cells by model-free calibrated half-bleaching. Nat Commun. 2022;13(1):7787.
- Kimura H, Sato Y. Imaging transcription elongation dynamics by new technologies unveils the organization of initiation and elongation in transcription factories. Curr Opin Cell Biol. 2022;74:71–79.
- Uchino S, Ito Y, Sato Y, et al. Live imaging of transcription sites using an elongating RNA polymerase II–specific probe. J Cell Bio. 2021;221(2):e202104134.
- Nguyen T, Li S, Chang J-H, et al. Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA. Nat Commun. 2022;13(1):3988.
- Keizer VIP, Grosse-Holz S, Woringer M, et al. Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics. Science. 2022;377(6605):489–495. DOI:10.1126/science.abi9810
- Qin W, Cho KF, Cavanagh PE, et al. Deciphering molecular interactions by proximity labeling. Nat Methods. 2021;116:1–11. InternetAvailable from. https://www.nature.com/articles/s41592-020-01010-5
- Trinkle-Mulcahy L. Recent advances in proximity-based labeling methods for interactome mapping. F1000Res. 2019;8:F1000. doi:10.12688/f1000research.16903.1. Faculty Rev-135.
- Alberti S, Dormann D. Liquid–liquid phase separation in disease. Ann Rev Genet. 2019;53(1):1–24.
- Kim J, Koo B-K, Knoblich JA. Human organoids: model systems for human biology and medicine. Nat Rev Mol Cell Bio. 2020;21(10):571–584.
- Beghin A, Grenci G, Rajendiran H, et al. High content 3D imaging method for quantitative characterization of organoid development and phenotype. bioRxiv. 2021;2021.03.26.437121.
- Coste A, Oktay MH, Condeelis JS, et al. Intravital imaging techniques for biomedical and clinical research. Cytom Part A. 2020;97(5):448–457.