Combinatorial function of transcription factors and cofactors

Current Opinion in Genetics and Development

Volumn 43, Issue , 2017, Pages 73-81

  Reiter, Franziska ^a   Wienerroither, Sebastian ^a   Stark, Alexander ^a  

^a RESEARCH INSTITUTE OF MOLECULAR PATHOLOGY   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; RNA POLYMERASE II; TRANSCRIPTION COFACTOR; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; PROTEIN BINDING;

ENHANCER REGION; ENZYME ACTIVITY; ENZYME MECHANISM; GENE CONTROL; NONHUMAN; PROMOTER REGION; PROTEIN DNA BINDING; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REVIEW; TRANSCRIPTION REGULATION; ANIMAL; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; GENETICS;

ANIMALS; ENHANCER ELEMENTS, GENETIC; GENE EXPRESSION REGULATION; PROMOTER REGIONS, GENETIC; PROTEIN BINDING; PROTEIN PROCESSING, POST-TRANSLATIONAL; RNA POLYMERASE II; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC;

EID: 85009837028     PISSN: 0959437X     EISSN: 18790380     Source Type: Journal    
DOI: 10.1016/j.gde.2016.12.007     Document Type: Review

References (93)

1. 1 Levine, M., Cattoglio, C., Tjian, R., Looping back to leap forward: transcription enters a new era. Cell 157 (2014), 13–25.
2. 2 Shlyueva, D., Stampfel, G., Stark, A., Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet 15 (2014), 272–286.
3. 3 Bhagwat, A.S., Vakoc, C.R., Targeting transcription factors in cancer. Trends Cancer 1 (2015), 53–65.
4. 4 Herz, H.-M., Hu, D., Shilatifard, A., Enhancer malfunction in cancer. Mol Cell 53 (2014), 859–866.
5. 5 Banerji, J., Rusconi, S., Schaffner, W., Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell 27 (1981), 299–308.
6. 6 Spitz, F., Furlong, E.E.M., Transcription factors: from enhancer binding to developmental control. Nat Rev Genet 13 (2012), 613–626.
7. 7 Takahashi, K., Yamanaka, S., Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 (2006), 663–676.
8. 8 Vierbuchen, T., Ostermeier, A., Pang, Z.P., Kokubu, Y., Südhof, T.C., Wernig, M., Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463 (2010), 1035–1041.
9. 9 Small, S., Blair, A., Levine, M., Regulation of even-skipped stripe 2 in the Drosophila embryo. EMBO J 11 (1992), 4047–4057.
10. 10 Swanson, C.I., Evans, N.C., Barolo, S., Structural rules and complex regulatory circuitry constrain expression of a Notch- and EGFR-regulated eye enhancer. Dev Cell 18 (2010), 359–370.
11. 11• Farley, E.K., Olson, K.M., Zhang, W., Brandt, A.J., Rokhsar, D.S., Levine, M.S., Suboptimization of developmental enhancers. Science 350 (2015), 325–328 Making use of the tissue specific expression of the Otx-a enhancer, the authors investigated the influence of motif spacing and quality on enhancer activity. They report a tradeoff between expression levels and tissue-specificity that evolution has exploited by mutations that altered the motif quality.
12. 12 Halfon, M.S., Carmena, A., Gisselbrecht, S., Sackerson, C.M., Jiménez, F., Baylies, M.K., Michelson, A.M., Ras pathway specificity is determined by the integration of multiple signal-activated and tissue-restricted transcription factors. Cell 103 (2000), 63–74.
13. 13 Barolo, S., Posakony, J.W., Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling. Genes Dev 16 (2002), 1167–1181.
14. 14 Thanos, D., Maniatis, T., Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell 83 (1995), 1091–1100.
15. 15 Yáñez-Cuna, J.O., Arnold, C.D., Stampfel, G., Boryń, L.M., Gerlach, D., Rath, M., Stark, A., Dissection of thousands of cell type-specific enhancers identifies dinucleotide repeat motifs as general enhancer features. Genome Res 24 (2014), 1147–1156.
16. 16 He, Q., Bardet, A.F., Patton, B., Purvis, J., Johnston, J., Paulson, A., Gogol, M., Stark, A., Zeitlinger, J., High conservation of transcription factor binding and evidence for combinatorial regulation across six Drosophila species. Nat Genet 43 (2011), 414–420.
17. 17 Villar, D., Berthelot, C., Aldridge, S., Rayner, T.F., Lukk, M., Pignatelli, M., Park, T.J., Deaville, R., Erichsen, J.T., Jasinska, A.J., et al. Enhancer evolution across 20 mammalian species. Cell 160 (2015), 554–566.
18. 18 Kasowski, M., Grubert, F., Heffelfinger, C., Hariharan, M., Asabere, A., Waszak, S.M., Habegger, L., Rozowsky, J., Shi, M., Urban, A.E., et al. Variation in transcription factor binding among humans. Science 328 (2010), 232–235.
19. 19 Zheng, W., Zhao, H., Mancera, E., Steinmetz, L.M., Snyder, M., Genetic analysis of variation in transcription factor binding in yeast. Nature 464 (2010), 1187–1191.
20. 20 Deplancke, B., Alpern, D., Gardeux, V., The genetics of transcription factor DNA binding variation. Cell 166 (2016), 538–554.
21. 21 Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y.C., Laslo, P., Cheng, J.X., Murre, C., Singh, H., Glass, C.K., Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell 38 (2010), 576–589.
22. 22 Yáñez-Cuna, J.O., Dinh, H.Q., Kvon, E.Z., Shlyueva, D., Stark, A., Uncovering cis-regulatory sequence requirements for context-specific transcription factor binding. Genome Res 22 (2012), 2018–2030.
23. 23 Barozzi, I., Simonatto, M., Bonifacio, S., Yang, L., Rohs, R., Ghisletti, S., Natoli, G., Coregulation of transcription factor binding and nucleosome occupancy through DNA features of mammalian enhancers. Mol Cell 54 (2014), 844–857.
24. 24 Foo, S.M., Sun, Y., Lim, B., Ziukaite, R., O'Brien, K., Nien, C.-Y., Kirov, N., Shvartsman, S.Y., Rushlow, C.A., Zelda potentiates morphogen activity by increasing chromatin accessibility. Curr Biol 24 (2014), 1341–1346.
25. 25• Schulz, K.N., Bondra, E.R., Moshe, A., Villalta, J.E., Lieb, J.D., Kaplan, T., McKay, D.J., Harrison, M.M., Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo. Genome Res 25 (2015), 1715–1726 The authors show the impact of the pioneer factor Zelda on DNA accessibility and binding of the TFs Dorsal and bicoid, proposing that Zelda in the early Drosophla embryo decreases the nucleosome barrier at enhancers, enables transcriptional activation, and functions as a pioneer factor.
26. 26• Sun, Y., Nien, C.-Y., Chen, K., Liu, H.-Y., Johnston, J., Zeitlinger, J., Rushlow, C., Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation. Genome Res 25 (2015), 1703–1714 The authors show the impact of the pioneer factor Zelda on DNA accessibility and binding of the TFs Dorsal and bicoid, proposing that Zelda in the early Drosophla embryo decreases the nucleosome barrier at enhancers, enables transcriptional activation, and functions as a pioneer factor.
27. 27 Sandmann, T., Jensen, L.J., Jakobsen, J.S., Karzynski, M.M., Eichenlaub, M.P., Bork, P., Furlong, E.E.M., A temporal map of transcription factor activity: mef2 directly regulates target genes at all stages of muscle development. Dev Cell 10 (2006), 797–807.
28. 28 Moyle-Heyrman, G., Tims, H.S., Widom, J., Structural constraints in collaborative competition of transcription factors against the nucleosome. J Mol Biol 412 (2011), 634–646.
29. 29 Lickwar, C.R., Mueller, F., Hanlon, S.E., McNally, J.G., Lieb, J.D., Genome-wide protein-DNA binding dynamics suggest a molecular clutch for transcription factor function. Nature 484 (2012), 251–255.
30. 30 Miller, J.A., Widom, J., Collaborative competition mechanism for gene activation in vivo. Mol Cell Biol 23 (2003), 1623–1632.
31. 31 Mirny, L.A., Nucleosome-mediated cooperativity between transcription factors. Proc Natl Acad Sci U S A 107 (2010), 22534–22539.
32. 32 Arnosti, D.N., Kulkarni, M.M., Transcriptional enhancers: intelligent enhanceosomes or flexible billboards?. J Cell Biochem 94 (2005), 890–898.
33. 33 Meireles-Filho, A.C.A., Stark, A., Comparative genomics of gene regulation-conservation and divergence of cis-regulatory information. Curr Opin Genet Dev 19 (2009), 565–570.
34. 34 Lee, D., Karchin, R., Beer, M.A., Discriminative prediction of mammalian enhancers from DNA sequence. Genome Res 21 (2011), 2167–2180.
35. 35• Ramachandran, S., Henikoff, S., Transcriptional regulators compete with nucleosomes post-replication. Cell 165 (2016), 580–592 The authors use metabolic labeling in a new method called MINCE-seq to map the genome-wide nucleosome landscape and its formation after DNA replication with high temporal resolution. Among other findings, the authors report that TFs compete with nucleosomes, thereby shaping nucleosome occupancy and DNA accessibility.
36. 36• Teves, S.S., An, L., Hansen, A.S., Xie, L., Darzacq, X., Tjian, R., A dynamic mode of mitotic bookmarking by transcription factors. eLife, 5, 2016, e22280 The authors use live imaging of TFs to demonstrate that the decade-long belief that TFs do not bind chromosomes during mitosis might be based on a fixation artifact and that many transcription factors stay bound to chromosomes.
37. 37 Kerppola, T.K., Curran, T., Fos-Jun heterodimers and Jun homodimers bend DNA in opposite orientations: implications for transcription factor cooperativity. Cell 66 (1991), 317–326.
38. 38• Jolma, A., Yin, Y., Nitta, K.R., Dave, K., Popov, A., Taipale, M., Enge, M., Kivioja, T., Morgunova, E., Taipale, J., DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature 527 (2015), 384–388 The authors determined and compared binding preferences of individual TFs and TF pairs. They report that pairs can bind to heterodimeric motifs which often differed from the motifs of the individual TFs. Interestingly, cooperativity was observed between TFs from different structural families.
39. 39 Panne, D., The enhanceosome. Curr Opin Struct Biol 18 (2008), 236–242.
40. 40 Liang, H.-L., Nien, C.-Y., Liu, H.-Y., Metzstein, M.M., Kirov, N., Rushlow, C., The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila. Nature 456 (2008), 400–403.
41. 41 Zaret, K.S., Carroll, J.S., Pioneer transcription factors: establishing competence for gene expression. Genes Dev 25 (2011), 2227–2241.
42. 42 Chen, J., Zhang, Z., Li, L., Chen, B.-C., Revyakin, A., Hajj, B., Legant, W., Dahan, M., Lionnet, T., Betzig, E., et al. Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell 156 (2014), 1274–1285.
43. 43 Soufi, A., Garcia, M.F., Jaroszewicz, A., Osman, N., Pellegrini, M., Zaret, K.S., Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161 (2015), 555–568.
44. 44 Lodish, H., Berk, A., Zipursky, S.L., et al. Eukaryotic Transcription Activators and Repressors. Molecular Cell Biology. 4th edition, 2000, W. H. Freeman, New York.
45. 45 Crocker, J., Ilsley, G.R., Stern, D.L., Quantitatively predictable control of Drosophila transcriptional enhancers in vivo with engineered transcription factors. Nat Genet 48 (2016), 292–298.
46. 46 Segal, E., Raveh-Sadka, T., Schroeder, M., Unnerstall, U., Gaul, U., Predicting expression patterns from regulatory sequence in Drosophila segmentation. Nature 451 (2008), 535–540.
47. 47 He, X., Samee, M.A.H., Blatti, C., Sinha, S., Thermodynamics-based models of transcriptional regulation by enhancers: the roles of synergistic activation, cooperative binding and short-range repression. PLoS Comput Biol, 6, 2010, e1000935.
48. 48 Smith, R.P., Taher, L., Patwardhan, R.P., Kim, M.J., Inoue, F., Shendure, J., Ovcharenko, I., Ahituv, N., Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model. Nat Genet 45:9 (2013), 1021–1028.
49. 49 Gertz, J., Siggia, E.D., Cohen, B.A., Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature 457 (2008), 215–219.
50. 50• Fiore, C., Cohen, B.A., Interactions between pluripotency factors specify cis-regulation in embryonic stem cells. Genome Res 26 (2016), 778–786 This study uses synthetic cis-regulatory elements (CREs) to test cooperativity between pluripotency factors in embryonic stem cells. It reports that combinations of different motifs and thus TFs are stronger than arrays of the same motif and finds that differences in arrangements can explain a large portion of the variability in expression between the CREs.
51. 51• Erceg, J., Saunders, T.E., Girardot, C., Devos, D.P., Hufnagel, L., Furlong, E.E.M., Subtle changes in motif positioning cause tissue-specific effects on robustness of an enhancer's activity. PLoS Genet, 10, 2014, e1004060 Using synthetic cis-regulatory modules (CRMs) with motifs for one or two different TFs, the authors addressed the differences in specificity and expression level of the reporter when varying number and orientation of the individual motifs. They show that already small differences can change the tissue specificity of a CRM.
52. 52 Ptashne, M., Gann, A., Transcriptional activation by recruitment. Nature 386 (1997), 569–577.
53. 53• Stampfel, G., Kazmar, T., Frank, O., Wienerroither, S., Reiter, F., Stark, A., Transcriptional regulators form diverse groups with context-dependent regulatory functions. Nature 528 (2015), 147–151 The authors assessed the regulatory function of Drosophila TFs and cofactors in an ectopic tethering reporter assay, and report that TFs and cofactors differ qualitatively and form 15 clusters with distinct regulatory functions.
54. 54• Keung, A.J., Bashor, C.J., Kiriakov, S., Collins, J.J., Khalil, A.S., Using targeted chromatin regulators to engineer combinatorial and spatial transcriptional regulation. Cell 158 (2014), 110–120 The authors tested ‘chromatin regulator-zinc finger’ fusions for their activity at a minimal-gene-locus to study chromatin regulators. Co-recruiting VP16 and the fusion library allowed the authors to identify cooperative effects between the chromatin regulator and the transcription factor.
55. 55 Zabidi, M.A., Stark, A., Regulatory enhancer-core-promoter communication via transcription factors and cofactors. Trends Genet 32 (2016), 801–814.
56. 56• Zabidi, M.A., Arnold, C.D., Schernhuber, K., Pagani, M., Rath, M., Frank, O., Stark, A., Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature 518 (2015), 556–559 The authors use the functional enhancer-activity assay STARR-seq to probe enhancer-core-promoter specificities and report that a sequence-encoded specificity discriminates housekeeping and developmental regulatory programs. Furthermore, differentially-enriched TFs suggest that the enhancer—core-promoter specificity is mediated by distinct regulatory proteins.
57. 57 Huisinga, K.L., Pugh, B.F., A genome-wide housekeeping role for TFIID and a highly regulated stress-related role for SAGA in Saccharomyces cerevisiae. Mol Cell 13 (2004), 573–585.
58. 58 Verfaillie, A., Svetlichnyy, D., Imrichova, H., Davie, K., Fiers, M., Kalender Atak, Z., Hulselmans, G., Christiaens, V., Aerts, S., Multiplex enhancer-reporter assays uncover unsophisticated TP53 enhancer logic. Genome Res 26 (2016), 882–895.
59. 59 Näär, A.M., Beaurang, P.A., Robinson, K.M., Oliner, J.D., Avizonis, D., Scheek, S., Zwicker, J., Kadonaga, J.T., Tjian, R., Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro. Genes Dev 12 (1998), 3020–3031.
60. 60 Hargreaves, D.C., Horng, T., Medzhitov, R., Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138 (2009), 129–145.
61. 61 Wienerroither, S., Shukla, P., Farlik, M., Majoros, A., Stych, B., Vogl, C., Cheon, H., Stark, G.R., Strobl, B., Müller, M., et al. Cooperative transcriptional activation of antimicrobial genes by STAT and NF-κB pathways by concerted recruitment of the mediator complex. Cell Rep 12 (2015), 300–312.
62. 62 Sims, R.J., Nishioka, K., Reinberg, D., Histone lysine methylation: a signature for chromatin function. Trends Genet 19 (2003), 629–639.
63. 63 Lee, K.K., Workman, J.L., Histone acetyltransferase complexes: one size doesn't fit all. Nat Rev Mol Cell Biol 8 (2007), 284–295.
64. 64 Domcke, S., Bardet, A.F., Adrian Ginno, P., Hartl, D., Burger, L., Schübeler, D., Competition between DNA methylation and transcription factors determines binding of NRF1. Nature 528 (2015), 575–579.
65. 65 Zhang, S., Cui, W., Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J Stem Cells 6 (2014), 305–311.
66. 66 Cheloufi, S., Elling, U., Hopfgartner, B., Jung, Y.L., Murn, J., Ninova, M., Hubmann, M., Badeaux, A.I., Euong Ang, C., Tenen, D., et al. The histone chaperone CAF-1 safeguards somatic cell identity. Nature 528 (2015), 218–224.
67. 67 Baud, V., Collares, D., Post-translational modifications of RelB NF-κB Subunit and associated functions. Cells, 5, 2016.
68. 68 Meek, D.W., Anderson, C.W., Posttranslational modification of p53: cooperative integrators of function. Cold Spring Harb Perspect Biol, 1, 2009, a000950.
69. 69 Liberman, A.C., Antunica-Noguerol, M., Arzt, E., Modulation of the glucocorticoid receptor activity by post-translational modifications. Nucl Recept Res 1 (2014), 1–15.
70. 70 Huang, B., Yang, X.-D., Zhou, M.-M., Ozato, K., Chen, L.-F., Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA. Mol Cell Biol 29 (2009), 1375–1387.
71. 71 Roe, J.-S., Mercan, F., Rivera, K., Pappin, D.J., Vakoc, C.R., BET bromodomain inhibition suppresses the function of hematopoietic transcription factors in acute myeloid leukemia. Mol Cell 58 (2015), 1028–1039.
72. 72 Sawicka, A., Hartl, D., Goiser, M., Pusch, O., Stocsits, R.R., Tamir, I.M., Mechtler, K., Seiser, C., H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress. Genome Res 24 (2014), 1808–1820.
73. 73 Pengelly, A.R., Copur, Ö., Jäckle, H., Herzig, A., Müller, J., A histone mutant reproduces the phenotype caused by loss of histone-modifying factor Polycomb. Science 339 (2013), 698–699.
74. 74 Hödl, M., Basler, K., Transcription in the absence of histone H3.2 and H3K4 methylation. Curr Biol 22 (2012), 2253–2257.
75. 75 Adelman, K., Lis, J.T., Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans. Nat Rev Genet 13 (2012), 720–731.
76. 76 Schröder, S., Herker, E., Itzen, F., He, D., Thomas, S., Gilchrist, D.A., Kaehlcke, K., Cho, S., Pollard, K.S., Capra, J.A., et al. Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells. Mol Cell 52 (2013), 314–324.
77. 77 Jang, M.K., Mochizuki, K., Zhou, M., Jeong, H.-S., Brady, J.N., Ozato, K., The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription. Mol Cell 19 (2005), 523–534.
78. 78 Yang, Z., Yik, J.H.N., Chen, R., He, N., Jang, M.K., Ozato, K., Zhou, Q., Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell 19 (2005), 535–545.
79. 79 Patel, M.C., Debrosse, M., Smith, M., Dey, A., Huynh, W., Sarai, N., Heightman, T.D., Tamura, T., Ozato, K., BRD4 coordinates recruitment of pause release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon-stimulated genes. Mol Cell Biol 33 (2013), 2497–2507.
80. 80 Takahashi, H., Parmely, T.J., Sato, S., Tomomori-Sato, C., Banks, C.A.S., Kong, S.E., Szutorisz, H., Swanson, S.K., Martin-Brown, S., Washburn, M.P., et al. Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 146 (2011), 92–104.
81. 81 Donner, A.J., Ebmeier, C.C., Taatjes, D.J., Espinosa, J.M., CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nat Struct Mol Biol 17 (2010), 194–201.
82. 82 Luo, Z., Lin, C., Shilatifard, A., The super elongation complex (SEC) family in transcriptional control. Nat Rev Mol Cell Biol 13 (2012), 543–547.
83. 83 Sexton, T., Yaffe, E., Kenigsberg, E., Bantignies, F., Leblanc, B., Hoichman, M., Parrinello, H., Tanay, A., Cavalli, G., Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148 (2012), 458–472.
84. 84 Dixon, J.R., Selvaraj, S., Yue, F., Kim, A., Li, Y., Shen, Y., Hu, M., Liu, J.S., Ren, B., Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485 (2012), 376–380.
85. 85 Nora, E.P., Lajoie, B.R., Schulz, E.G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N.L., Meisig, J., Sedat, J., et al. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485 (2012), 381–385.
86. 86 Lupiáñez, D.G., Kraft, K., Heinrich, V., Krawitz, P., Brancati, F., Klopocki, E., Horn, D., Kayserili, H., Opitz, J.M., Laxova, R., et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161 (2015), 1012–1025.
87. 87• Fukaya, T., Lim, B., Levine, M., Enhancer control of transcriptional bursting. Cell 166 (2016), 358–368 The authors used live imaging to analyze the relationship between enhancers of different strengths and gene expression levels with transcriptional bursting. They demonstrated that one enhancer can produce simultaneous burst from two independent promoters, suggesting a more flexible form of enhancer—core-promoter communication.
88. 88 Brangwynne, C.P., Eckmann, C.R., Courson, D.S., Rybarska, A., Hoege, C., Gharakhani, J., Jülicher, F., Hyman, A.A., Germline P granules are liquid droplets that localize by controlled dissolution/condensation. Science 324 (2009), 1729–1732.
89. 89 Kroschwald, S., Maharana, S., Mateju, D., Malinovska, L., Nüske, E., Poser, I., Richter, D., Alberti, S., Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules. eLife, 4, 2015, e06807.
90. 90 Feric, M., Vaidya, N., Harmon, T.S., Mitrea, D.M., Zhu, L., Richardson, T.M., Kriwacki, R.W., Pappu, R.V., Brangwynne, C.P., Coexisting liquid phases underlie nucleolar subcompartments. Cell 165 (2016), 1686–1697.
91. 91 Mitrea, D.M., Kriwacki, R.W., Phase separation in biology: functional organization of a higher order. Cell Commun Signal, 14, 2016, 1.
92. 92 Latchman, D.S., Activation of gene expression by transcription factors. Eukaryotic Transcription Factors, 2008, Elsevier, 161–228.
93. 93 Erkina, T.Y., Erkine, A.M., Nucleosome distortion as a possible mechanism of transcription activation domain function. Epigenet Chromatin, 9, 2016, 40.