Abstract
Eukaryotic transcription factors are versatile mediators of specificity in gene regulation. This versatility is achieved through mutual specification by context-specific DNA binding on the one hand, and identity-specific protein-protein partnerships on the other. This interactivity, known as combinatorial control, enables a repertoire of complex transcriptional outputs that are qualitatively disjoint, or non-continuum, with respect to binding affinity. This feature contrasts starkly with prokaryotic gene regulators, whose activities in general vary quantitatively in step with binding affinity. Biophysical studies on prokaryotic model systems and more recent investigations on transcription factors highlight an important role for folded state dynamics and molecular hydration in protein/DNA recognition. Analysis of molecular models of combinatorial control and recent literature in low-affinity gene regulation suggest that transcription factors harbor unique conformational dynamics that are inaccessible or unused by prokaryotic DNA-binding proteins. Thus, understanding the intrinsic dynamics involved in DNA binding and co-regulator recruitment appears to be a key to understanding how transcription factors mediate non-continuum outcomes in eukaryotic gene expression, and how such capability might have evolved from ancient, structurally conserved counterparts.
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References
Albrecht AV, Kim HM, Poon GMK (2018) Mapping interfacial hydration in ETS-family transcription factor complexes with DNA: a chimeric approach. Nucleic Acids Res 46(20):10577–10588. https://doi.org/10.1093/nar/gky894
Alvarez LD, Presman DM, Pecci A (2017) Molecular dynamics simulations of the glucocorticoid receptor DNA-binding domain suggest a role of the lever-arm mobility in transcriptional output. PLoS One 12(12):e0189588. https://doi.org/10.1371/journal.pone.0189588
Aravind L, Anantharaman V, Balaji S, Babu MM, Iyer LM (2005) The many faces of the helix-turn-helix domain: transcription regulation and beyond. FEMS Microbiol Rev 29(2):231–262. https://doi.org/10.1016/j.femsre.2004.12.008
Assa-Munt N, Mortishire-Smith RJ, Aurora R, Herr W, Wright PE (1993) The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain. Cell 73(1):193–205. https://doi.org/10.1016/0092-8674(93)90171-l
Baetu TM (2011) A defense of syntax-based gene concepts in Postgenomics: genes as modular subroutines in the master genomic program. Philos Sci 78(5):712–723. https://doi.org/10.1086/662261
Ballare C, Castellano G, Gaveglia L, Althammer S, Gonzalez-Vallinas J, Eyras E, Le Dily F, Zaurin R, Soronellas D, Vicent GP, Beato M (2013) Nucleosome-driven transcription factor binding and gene regulation. Mol Cell 49(1):67–79. https://doi.org/10.1016/j.molcel.2012.10.019
Barolo S (2016) How to tune an enhancer. Proc Natl Acad Sci U S A 113(23):6330–6331. https://doi.org/10.1073/pnas.1606109113
Breiten B, Lockett MR, Sherman W, Fujita S, Al-Sayah M, Lange H, Bowers CM, Heroux A, Krilov G, Whitesides GM (2013) Water networks contribute to enthalpy/entropy compensation in protein-ligand binding. J Am Chem Soc 135(41):15579–15584. https://doi.org/10.1021/ja4075776
Brüssow H, Hendrix RW (2002) Phage genomics. Cell 108(1):13–16. https://doi.org/10.1016/s0092-8674(01)00637-7
Buchan JR (2014) mRNP granules. Assembly, function, and connections with disease. RNA Biol 11(8):1019–1030. https://doi.org/10.4161/15476286.2014.972208
Burton ZF, Opron K, Wei G, Geiger JH (2016) A model for genesis of transcription systems. Transcription 7(1):1–13. https://doi.org/10.1080/21541264.2015.1128518
Cary GA, Cheatle Jarvela AM, Francolini RD, Hinman VF (2017) Genome-wide use of high- and low-affinity Tbrain transcription factor binding sites during echinoderm development. Proc Natl Acad Sci U S A 114(23):5854–5861. https://doi.org/10.1073/pnas.1610611114
Chalikian TV (2003) Volumetric properties of proteins. Annu Rev Biophys Biomol Struct 32:207–235. https://doi.org/10.1146/annurev.biophys.32.110601.141709
Chalikian TV, Macgregor RB (2007) Nucleic acid hydration: a volumetric perspective. Phys Life Rev 4(2):91–115. https://doi.org/10.1016/j.plrev.2006.11.001
Changeux JP, Edelstein S (2011) Conformational selection or induced fit? 50 years of debate resolved. F1000 Biol Rep 3:19. https://doi.org/10.3410/B3-19
Charoensawan V, Wilson D, Teichmann SA (2010) Genomic repertoires of DNA-binding transcription factors across the tree of life. Nucleic Acids Res 38(21):7364–7377. https://doi.org/10.1093/nar/gkq617
Cinar H, Fetahaj Z, Cinar S, Vernon RM, Chan HS, Winter RHA (2019) Temperature, hydrostatic pressure, and Osmolyte effects on liquid-liquid phase separation in protein condensates: physical chemistry and biological implications. Chemistry 25(57):13049–13069. https://doi.org/10.1002/chem.201902210
Cogoi S, Paramasivam M, Membrino A, Yokoyama KK, Xodo LE (2010) The KRAS promoter responds to Myc-associated zinc finger and poly(ADP-ribose) polymerase 1 proteins, which recognize a critical quadruplex-forming GA-element. J Biol Chem 285(29):22003–22016. https://doi.org/10.1074/jbc.M110.101923
Cooper A (1976) Thermodynamic fluctuations in protein molecules. Proc Natl Acad Sci U S A 73(8):2740–2741. https://doi.org/10.1073/pnas.73.8.2740
Cooper A (1984) Protein fluctuations and the thermodynamic uncertainty principle. Prog Biophys Mol Biol 44(3):181–214. https://doi.org/10.1016/0079-6107(84)90008-7
Crocker J, Abe N, Rinaldi L, McGregor AP, Frankel N, Wang S, Alsawadi A, Valenti P, Plaza S, Payre F, Mann RS, Stern DL (2015) Low affinity binding site clusters confer hox specificity and regulatory robustness. Cell 160(1–2):191–203. https://doi.org/10.1016/j.cell.2014.11.041
Crocker J, Noon EP, Stern DL (2016) The soft touch: low-affinity transcription factor binding sites in development and evolution. Curr Top Dev Biol 117:455–469. https://doi.org/10.1016/bs.ctdb.2015.11.018
de Mendoza A, Sebe-Pedros A, Sestak MS, Matejcic M, Torruella G, Domazet-Loso T, Ruiz-Trillo I (2013) Transcription factor evolution in eukaryotes and the assembly of the regulatory toolkit in multicellular lineages. Proc Natl Acad Sci U S A 110(50):E4858–E4866. https://doi.org/10.1073/pnas.1311818110
Degnan BM, Degnan SM, Naganuma T, Morse DE (1993) The ets multigene family is conserved throughout the Metazoa. Nucleic Acids Res 21(15):3479–3484
Deniz AA, Mukhopadhyay S, Lemke EA (2008) Single-molecule biophysics: at the interface of biology, physics and chemistry. J R Soc Interface 5(18):15–45. https://doi.org/10.1098/rsif.2007.1021
Duboue-Dijon E, Fogarty AC, Hynes JT, Laage D (2016) Dynamical disorder in the DNA hydration Shell. J Am Chem Soc 138(24):7610–7620. https://doi.org/10.1021/jacs.6b02715
Eaves JD, Loparo JJ, Fecko CJ, Roberts ST, Tokmakoff A, Geissler PL (2005) Hydrogen bonds in liquid water are broken only fleetingly. Proc Natl Acad Sci U S A 102(37):13019–13022. https://doi.org/10.1073/pnas.0505125102
Farley EK, Olson KM, Zhang W, Brandt AJ, Rokhsar DS, Levine MS (2015) Suboptimization of developmental enhancers. Science 350(6258):325–328. https://doi.org/10.1126/science.aac6948
Farley EK, Olson KM, Zhang W, Rokhsar DS, Levine MS (2016) Syntax compensates for poor binding sites to encode tissue specificity of developmental enhancers. Proc Natl Acad Sci U S A 113(23):6508–6513. https://doi.org/10.1073/pnas.1605085113
Fox JM, Zhao M, Fink MJ, Kang K, Whitesides GM (2018) The molecular origin of enthalpy/entropy compensation in biomolecular recognition. Annu Rev Biophys 47:223–250. https://doi.org/10.1146/annurev-biophys-070816-033743
Gallo PN, Iovine JC, Nucci NV (2018) Toward comprehensive measurement of protein hydration dynamics: facilitation of NMR-based methods by reverse micelle encapsulation. Methods 148:146–153. https://doi.org/10.1016/j.ymeth.2018.07.008
Gao J, Zybailov BL, Byrd AK, Griffin WC, Chib S, Mackintosh SG, Tackett AJ, Raney KD (2015) Yeast transcription co-activator Sub1 and its human homolog PC4 preferentially bind to G-quadruplex DNA. Chem Commun (Camb) 51(33):7242–7244. https://doi.org/10.1039/c5cc00742a
Garvie CW, Pufall MA, Graves BJ, Wolberger C (2002) Structural analysis of the autoinhibition of Ets-1 and its role in protein partnerships. J Biol Chem 277(47):45529–45536. https://doi.org/10.1074/jbc.M206327200
Gaudet J, Mango SE (2002) Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Science 295(5556):821–825. https://doi.org/10.1126/science.1065175
Glasmacher E, Agrawal S, Chang AB, Murphy TL, Zeng W, Vander Lugt B, Khan AA, Ciofani M, Spooner CJ, Rutz S, Hackney J, Nurieva R, Escalante CR, Ouyang W, Littman DR, Murphy KM, Singh H (2012) A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science 338(6109):975–980. https://doi.org/10.1126/science.1228309
Goodsell DS (1991) Inside a living cell. Trends Biochem Sci 16(6):203–206
Grossman SR, Engreitz J, Ray JP, Nguyen TH, Hacohen N, Lander ES (2018) Positional specificity of different transcription factor classes within enhancers. Proc Natl Acad Sci U S A 115(30):E7222–E7230. https://doi.org/10.1073/pnas.1804663115
Guo X, Bulyk ML, Hartemink AJ (2012) Intrinsic disorder within and flanking the DNA-binding domains of human transcription factors. Pac Symp Biocomput:104–115. https://doi.org/10.1142/9789814366496_0011
Handberg-Thorsager M, Gutierrez-Mazariegos J, Arold ST, Kumar Nadendla E, Bertucci PY, Germain P, Tomancak P, Pierzchalski K, Jones JW, Albalat R, Kane MA, Bourguet W, Laudet V, Arendt D, Schubert M (2018) The ancestral retinoic acid receptor was a low-affinity sensor triggering neuronal differentiation. Sci Adv 4(2):eaao1261. https://doi.org/10.1126/sciadv.aao1261
He HH, Meyer CA, Shin H, Bailey ST, Wei G, Wang Q, Zhang Y, Xu K, Ni M, Lupien M, Mieczkowski P, Lieb JD, Zhao K, Brown M, Liu XS (2010) Nucleosome dynamics define transcriptional enhancers. Nat Genet 42(4):343–347. https://doi.org/10.1038/ng.545
Herr W, Cleary MA (1995) The POU domain: versatility in transcriptional regulation by a flexible two-in-one DNA-binding domain. Genes Dev 9(14):1679–1693. https://doi.org/10.1101/gad.9.14.1679
Hosokawa H, Ungerback J, Wang X, Matsumoto M, Nakayama KI, Cohen SM, Tanaka T, Rothenberg EV (2018) Transcription factor PU.1 represses and activates gene expression in early T cells by redirecting partner transcription factor binding. Immunity 49(4):782. https://doi.org/10.1016/j.immuni.2018.09.019
Huang K, Xhani S, Albrecht AV, Ha VLT, Esaki S, Poon GMK (2019) Mechanism of cognate sequence discrimination by the ETS-family transcription factor ETS-1. J Biol Chem 294(25):9666–9678. https://doi.org/10.1074/jbc.RA119.007866
Hudson WH, Youn C, Ortlund EA (2013) The structural basis of direct glucocorticoid-mediated transrepression. Nat Struct Mol Biol 20(1):53–58. https://doi.org/10.1038/nsmb.2456
Ingraham HA, Flynn SE, Voss JW, Albert VR, Kapiloff MS, Wilson L, Rosenfeld MG (1990) The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions. Cell 61(6):1021–1033. https://doi.org/10.1016/0092-8674(90)90067-o
Ishimoto C, Tanaka T (1977) Critical behavior of a binary mixture of protein and salt water. Phys Rev Lett 39(8):474–477. https://doi.org/10.1103/PhysRevLett.39.474
Iwata A, Durai V, Tussiwand R, Briseño CG, Wu X, Grajales-Reyes GE, Egawa T, Murphy TL, Murphy KM (2017) Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF–IRF4 transcription factor complex. Nat Immunol 18(5):563–572. https://doi.org/10.1038/ni.3714
Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK (1997) Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev 11(2):198–212. https://doi.org/10.1101/gad.11.2.198
Jiang J, Levine M (1993) Binding affinities and cooperative interactions with bHLH activators delimit threshold responses to the dorsal gradient morphogen. Cell 72(5):741–752
Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J (2015) DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature 527(7578):384–388. https://doi.org/10.1038/nature15518
Joyce AP, Zhang C, Bradley P, Havranek JJ (2015) Structure-based modeling of protein: DNA specificity. Brief Funct Genomics 14(1):39–49. https://doi.org/10.1093/bfgp/elu044
Kalodimos CG, Bonvin AM, Salinas RK, Wechselberger R, Boelens R, Kaptein R (2002) Plasticity in protein-DNA recognition: lac repressor interacts with its natural operator 01 through alternative conformations of its DNA-binding domain. EMBO J 21(12):2866–2876. https://doi.org/10.1093/emboj/cdf318
Kalodimos CG, Biris N, Bonvin AM, Levandoski MM, Guennuegues M, Boelens R, Kaptein R (2004a) Structure and flexibility adaptation in nonspecific and specific protein-DNA complexes. Science 305(5682):386–389. https://doi.org/10.1126/science.1097064
Kalodimos CG, Boelens R, Kaptein R (2004b) Toward an integrated model of protein-DNA recognition as inferred from NMR studies on the Lac repressor system. Chem Rev 104(8):3567–3586. https://doi.org/10.1021/cr0304065
Kleckner IR, Foster MP (2011) An introduction to NMR-based approaches for measuring protein dynamics. Biochim Biophys Acta 1814(8):942–968. https://doi.org/10.1016/j.bbapap.2010.10.012
Kribelbauer JF, Rastogi C, Bussemaker HJ, Mann RS (2019) Low-affinity binding sites and the transcription factor specificity paradox in eukaryotes. Annu Rev Cell Dev Biol 35:357–379. https://doi.org/10.1146/annurev-cellbio-100617-062719
Krishnamoorthy V, Kannanganat S, Maienschein-Cline M, Cook SL, Chen J, Bahroos N, Sievert E, Corse E, Chong A, Sciammas R (2017) The IRF4 gene regulatory module functions as a read-write integrator to dynamically coordinate T helper cell fate. Immunity 47(3):481–497 e487. https://doi.org/10.1016/j.immuni.2017.09.001
Kyrmizi I, Hatzis P, Katrakili N, Tronche F, Gonzalez FJ, Talianidis I (2006) Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev 20(16):2293–2305. https://doi.org/10.1101/gad.390906
Laage D, Hynes JT (2006) A molecular jump mechanism of water reorientation. Science 311(5762):832–835. https://doi.org/10.1126/science.1122154
Laage D, Elsaesser T, Hynes JT (2017) Water dynamics in the hydration shells of biomolecules. Chem Rev 117(16):10694–10725. https://doi.org/10.1021/acs.chemrev.6b00765
Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, Chen X, Taipale J, Hughes TR, Weirauch MT (2018) The human transcription factors. Cell 172(4):650–665. https://doi.org/10.1016/j.cell.2018.01.029
Landsman D, Wolffe AP (1995) Common sequence and structural features in the heat-shock factor and Ets families of DNA-binding domains. Trends Biochem Sci 20(6):225–226. https://doi.org/10.1016/S0968-0004(00)89021-0
Lawson CL, Swigon D, Murakami KS, Darst SA, Berman HM, Ebright RH (2004) Catabolite activator protein: DNA binding and transcription activation. Curr Opin Struct Biol 14(1):10–20. https://doi.org/10.1016/j.sbi.2004.01.012
Lefstin JA, Yamamoto KR (1998) Allosteric effects of DNA on transcriptional regulators. Nature 392(6679):885–888. https://doi.org/10.1038/31860
Leung TH, Hoffmann A, Baltimore D (2004) One nucleotide in a kappaB site can determine cofactor specificity for NF-kappaB dimers. Cell 118(4):453–464. https://doi.org/10.1016/j.cell.2004.08.007
Li XY, Thomas S, Sabo PJ, Eisen MB, Stamatoyannopoulos JA, Biggin MD (2011) The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding. Genome Biol 12(4):ARTN R34671186/gb-2011-12-4-r34
Liang H, Olejniczak ET, Mao X, Nettesheim DG, Yu L, Thompson CB, Fesik SW (1994) The secondary structure of the ets domain of human Fli-1 resembles that of the helix-turn-helix DNA-binding motif of the Escherichia coli catabolite gene activator protein. Proc Natl Acad Sci U S A 91(24):11655–11659
Liu J, Perumal NB, Oldfield CJ, Su EW, Uversky VN, Dunker AK (2006) Intrinsic disorder in transcription factors. Biochemistry 45(22):6873–6888. https://doi.org/10.1021/bi0602718
Liu CF, Brandt GS, Hoang QQ, Naumova N, Lazarevic V, Hwang ES, Dekker J, Glimcher LH, Ringe D, Petsko GA (2016a) Crystal structure of the DNA binding domain of the transcription factor T-bet suggests simultaneous recognition of distant genome sites. Proc Natl Acad Sci U S A 113(43):E6572–E6581. https://doi.org/10.1073/pnas.1613914113
Liu X, Speckhard DC, Shepherd TR, Sun YJ, Hengel SR, Yu L, Fowler CA, Gakhar L, Fuentes EJ (2016b) Distinct roles for conformational dynamics in protein-ligand interactions. Structure 24(12):2053–2066. https://doi.org/10.1016/j.str.2016.08.019
Luisi BF, Xu WX, Otwinowski Z, Freedman LP, Yamamoto KR, Sigler PB (1991) Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA. Nature 352(6335):497–505. https://doi.org/10.1038/352497a0
Lynch TW, Sligar SG (2002) Experimental and theoretical high pressure strategies for investigating protein-nucleic acid assemblies. Biochim Biophys Acta 1595(1–2):277–282. https://doi.org/10.1016/s0167-4838(01)00350-8
Macgregor RB (2002) The interactions of nucleic acids at elevated hydrostatic pressure. Biochim Biophys Acta Protein Struct Mol Enzymol 1595(1–2):266–276. https://doi.org/10.1016/s0167-4838(01)00349-1
Magnani L, Eeckhoute J, Lupien M (2011) Pioneer factors: directing transcriptional regulators within the chromatin environment. Trends Genet 27(11):465–474. https://doi.org/10.1016/j.tig.2011.07.002
Meijsing SH, Pufall MA, So AY, Bates DL, Chen L, Yamamoto KR (2009) DNA binding site sequence directs glucocorticoid receptor structure and activity. Science 324(5925):407–410. https://doi.org/10.1126/science.1164265
Merino E, Jensen RA, Yanofsky C (2008) Evolution of bacterial trp operons and their regulation. Curr Opin Microbiol 11(2):78–86. https://doi.org/10.1016/j.mib.2008.02.005
Minezaki Y, Homma K, Kinjo AR, Nishikawa K (2006) Human transcription factors contain a high fraction of intrinsically disordered regions essential for transcriptional regulation. J Mol Biol 359(4):1137–1149. https://doi.org/10.1016/j.jmb.2006.04.016
Mohaghegh N, Bray D, Keenan J, Penvose A, Andrilenas KK, Ramlall V, Siggers T (2019) NextPBM: a platform to study cell-specific transcription factor binding and cooperativity. Nucleic Acids Res 47(6):e31. https://doi.org/10.1093/nar/gkz020
Monod J, Wyman J, Changeux JP (1965) On the nature of allosteric transitions: a plausible model. J Mol Biol 12:88–118. https://doi.org/10.1016/s0022-2836(65)80285-6
Nakasako M (2004) Water-protein interactions from high-resolution protein crystallography. Philos Trans R Soc Lond Ser B Biol Sci 359(1448):1191–1204; discussion 1204-1196. https://doi.org/10.1098/rstb.2004.1498
Nussinov R, Ma B, Tsai CJ (2014) Multiple conformational selection and induced fit events take place in allosteric propagation. Biophys Chem 186:22–30. https://doi.org/10.1016/j.bpc.2013.10.002
Orkin SH, Zon LI (2008) Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132(4):631–644. https://doi.org/10.1016/j.cell.2008.01.025
Pan Y, Tsai CJ, Ma B, Nussinov R (2009) How do transcription factors select specific binding sites in the genome? Nat Struct Mol Biol 16(11):1118–1120. https://doi.org/10.1038/nsmb1109-1118
Pan Y, Tsai CJ, Ma B, Nussinov R (2010) Mechanisms of transcription factor selectivity. Trends Genet 26(2):75–83. https://doi.org/10.1016/j.tig.2009.12.003
Pan A, Biswas T, Rakshit AK, Moulik SP (2015) Enthalpy-Entropy Compensation (EEC) effect: a revisit. J Phys Chem B 119(52):15876–15884. https://doi.org/10.1021/acs.jpcb.5b09925
Pan AC, Jacobson D, Yatsenko K, Sritharan D, Weinreich TM, Shaw DE (2019) Atomic-level characterization of protein-protein association. Proc Natl Acad Sci U S A 116(10):4244–4249. https://doi.org/10.1073/pnas.1815431116
Panne D (2008) The enhanceosome. Curr Opin Struct Biol 18(2):236–242. https://doi.org/10.1016/j.sbi.2007.12.002
Panne D, Maniatis T, Harrison SC (2007) An atomic model of the interferon-beta enhanceosome. Cell 129(6):1111–1123. https://doi.org/10.1016/j.cell.2007.05.019
Parsegian VA, Rau DC (1984) Water near intracellular surfaces. J Cell Biol 99(1 Pt 2):196s–200s. https://doi.org/10.1083/jcb.99.1.196s
Parsegian VA, Rand RP, Rau DC (1995) Macromolecules and water: probing with osmotic stress. Methods Enzymol 259:43–94
Parsonnet NV, Lammer NC, Holmes ZE, Batey RT, Wuttke DS (2019) The glucocorticoid receptor DNA-binding domain recognizes RNA hairpin structures with high affinity. Nucleic Acids Res 47(15):8180–8192. https://doi.org/10.1093/nar/gkz486
Persson F, Soderhjelm P, Halle B (2018) The spatial range of protein hydration. J Chem Phys 148(21):215104. https://doi.org/10.1063/1.5031005
Popovych N, Sun S, Ebright RH, Kalodimos CG (2006) Dynamically driven protein allostery. Nat Struct Mol Biol 13(9):831–838. https://doi.org/10.1038/nsmb1132
Preger-Ben Noon E, Sabaris G, Ortiz DM, Sager J, Liebowitz A, Stern DL, Frankel N (2018) Comprehensive analysis of a cis-regulatory region reveals pleiotropy in enhancer function. Cell Rep 22(11):3021–3031. https://doi.org/10.1016/j.celrep.2018.02.073
Purslow JA, Khatiwada B, Bayro MJ, Venditti V (2020) NMR methods for structural characterization of protein-protein complexes. Front Mol Biosci 7:9. https://doi.org/10.3389/fmolb.2020.00009
Ramos AI, Barolo S (2013) Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution. Philos Trans R Soc Lond Ser B Biol Sci 368(1632):20130018. https://doi.org/10.1098/rstb.2013.0018
Rand RP, Parsegian VA, Rau DC (2000) Intracellular osmotic action. Cell Mol Life Sci 57(7):1018–1032. https://doi.org/10.1007/PL00000742
Rastogi C, Rube HT, Kribelbauer JF, Crocker J, Loker RE, Martini GD, Laptenko O, Freed-Pastor WA, Prives C, Stern DL, Mann RS, Bussemaker HJ (2018) Accurate and sensitive quantification of protein-DNA binding affinity. Proc Natl Acad Sci U S A 115(16):E3692–E3701. https://doi.org/10.1073/pnas.1714376115
Remenyi A, Tomilin A, Pohl E, Lins K, Philippsen A, Reinbold R, Scholer HR, Wilmanns M (2001) Differential dimer activities of the transcription factor Oct-1 by DNA-induced interface swapping. Mol Cell 8(3):569–580. https://doi.org/10.1016/s1097-2765(01)00336-7
Remenyi A, Scholer HR, Wilmanns M (2004) Combinatorial control of gene expression. Nat Struct Mol Biol 11(9):812–815. https://doi.org/10.1038/nsmb820
Rhine K, Vidaurre V, Myong S (2020) RNA droplets. Annu Rev Biophys 49:247–265. https://doi.org/10.1146/annurev-biophys-052118-115508
Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS (2010) Origins of specificity in protein-DNA recognition. Annu Rev Biochem 79:233–269. https://doi.org/10.1146/annurev-biochem-060408-091030
Royer CA, Winter R (2009) Volumetric properties of proteins and the role of solvent in conformational dynamics. In: Kuwajima K, Goto Y, Hirata F, Kataoka M, Terazima M (eds) Water and biomolecules. Biological and medical physics, biomedical engineering. Springer, Berlin/Heidelberg, pp 173–186. https://doi.org/10.1007/978-3-540-88787-4_9
Rubin MM, Changeux JP (1966) On the nature of allosteric transitions: implications of non-exclusive ligand binding. J Mol Biol 21(2):265–274. https://doi.org/10.1016/0022-2836(66)90097-0
Santoro N, Johansson N, Thiele DJ (1998) Heat shock element architecture is an important determinant in the temperature and transactivation domain requirements for heat shock transcription factor. Mol Cell Biol 18(11):6340–6352. https://doi.org/10.1128/mcb.18.11.6340
Sauer RT, Yocum RR, Doolittle RF, Lewis M, Pabo CO (1982) Homology among DNA-binding proteins suggests use of a conserved super-secondary structure. Nature 298(5873):447–451. https://doi.org/10.1038/298447a0
Schmitz JF, Zimmer F, Bornberg-Bauer E (2016) Mechanisms of transcription factor evolution in Metazoa. Nucleic Acids Res 44(13):6287–6297. https://doi.org/10.1093/nar/gkw492
Scully KM, Jacobson EM, Jepsen K, Lunyak V, Viadiu H, Carriere C, Rose DW, Hooshmand F, Aggarwal AK, Rosenfeld MG (2000) Allosteric effects of Pit-1 DNA sites on long-term repression in cell type specification. Science 290(5494):1127–1131. https://doi.org/10.1126/science.290.5494.1127
Sebe-Pedros A, Ariza-Cosano A, Weirauch MT, Leininger S, Yang A, Torruella G, Adamski M, Adamska M, Hughes TR, Gomez-Skarmeta JL, Ruiz-Trillo I (2013) Early evolution of the T-box transcription factor family. Proc Natl Acad Sci U S A 110(40):16050–16055. https://doi.org/10.1073/pnas.1309748110
Sikorska N, Sexton T (2020) Defining functionally relevant spatial chromatin domains: it is a TAD complicated. J Mol Biol 432(3):653–664. https://doi.org/10.1016/j.jmb.2019.12.006
Silva JL, Foguel D, Royer CA (2001) Pressure provides new insights into protein folding, dynamics and structure. Trends Biochem Sci 26(10):612–618. https://doi.org/10.1016/s0968-0004(01)01949-1
Singh GP, Dash D (2007) Intrinsic disorder in yeast transcriptional regulatory network. Proteins 68(3):602–605. https://doi.org/10.1002/prot.21497
Slattery M, Zhou T, Yang L, Dantas Machado AC, Gordan R, Rohs R (2014) Absence of a simple code: how transcription factors read the genome. Trends Biochem Sci 39(9):381–399. https://doi.org/10.1016/j.tibs.2014.07.002
Soufi A, Garcia MF, Jaroszewicz A, Osman N, Pellegrini M, Zaret KS (2015) Pioneer transcription factors target partial DNA motifs on nucleosomes to initiate reprogramming. Cell 161(3):555–568. https://doi.org/10.1016/j.cell.2015.03.017
Spolar RS, Record MT Jr (1994) Coupling of local folding to site-specific binding of proteins to DNA. Science 263(5148):777–784
Sturm RA, Herr W (1988) The POU domain is a bipartite DNA-binding structure. Nature 336(6199):601–604. https://doi.org/10.1038/336601a0
Szabo Q, Bantignies F, Cavalli G (2019) Principles of genome folding into topologically associating domains. Sci Adv 5(4):eaaw1668. https://doi.org/10.1126/sciadv.aaw1668
Thomas-Chollier M, Watson LC, Cooper SB, Pufall MA, Liu JS, Borzym K, Vingron M, Yamamoto KR, Meijsing SH (2013) A naturally occurring insertion of a single amino acid rewires transcriptional regulation by glucocorticoid receptor isoforms. Proc Natl Acad Sci U S A 110(44):17826–17831. https://doi.org/10.1073/pnas.1316235110
Tzeng SR, Kalodimos CG (2012) Protein activity regulation by conformational entropy. Nature 488(7410):236–240. https://doi.org/10.1038/nature11271
Uversky VN (2017) Intrinsically disordered proteins in overcrowded milieu: membrane-less organelles, phase separation, and intrinsic disorder. Curr Opin Struct Biol 44:18–30. https://doi.org/10.1016/j.sbi.2016.10.015
van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, Fuxreiter M, Gough J, Gsponer J, Jones DT, Kim PM, Kriwacki RW, Oldfield CJ, Pappu RV, Tompa P, Uversky VN, Wright PE, Babu MM (2014) Classification of intrinsically disordered regions and proteins. Chem Rev 114(13):6589–6631. https://doi.org/10.1021/cr400525m
van Hijum SA, Medema MH, Kuipers OP (2009) Mechanisms and evolution of control logic in prokaryotic transcriptional regulation. Microbiol Mol Biol Rev 73(3):481–509, Table of Contents. https://doi.org/10.1128/MMBR.00037-08
van Leeuwen HC, Strating MJ, Rensen M, de Laat W, van der Vliet PC (1997) Linker length and composition influence the flexibility of Oct-1 DNA binding. EMBO J 16(8):2043–2053. https://doi.org/10.1093/emboj/16.8.2043
Vandevyver S, Dejager L, Libert C (2014) Comprehensive overview of the structure and regulation of the glucocorticoid receptor. Endocr Rev 35(4):671–693. https://doi.org/10.1210/er.2014-1010
Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM (2009) A census of human transcription factors: function, expression and evolution. Nat Rev Genet 10(4):252–263. https://doi.org/10.1038/nrg2538
Villa E, Balaeff A, Schulten K (2005) Structural dynamics of the lac repressor-DNA complex revealed by a multiscale simulation. Proc Natl Acad Sci U S A 102(19):6783–6788. https://doi.org/10.1073/pnas.0409387102
Vogt AD, Di Cera E (2012) Conformational selection or induced fit? A critical appraisal of the kinetic mechanism. Biochemistry 51(30):5894–5902. https://doi.org/10.1021/bi3006913
Vogt AD, Di Cera E (2013) Conformational selection is a dominant mechanism of ligand binding. Biochemistry 52(34):5723–5729. https://doi.org/10.1021/bi400929b
Vogt AD, Pozzi N, Chen Z, Di Cera E (2014) Essential role of conformational selection in ligand binding. Biophys Chem 186:13–21. https://doi.org/10.1016/j.bpc.2013.09.003
Wang Z, Zhang Q (2009) Genome-wide identification and evolutionary analysis of the animal specific ETS transcription factor family. Evol Bioinformatics Online 5:119–131
Wang S, Linde MH, Munde M, Carvalho VD, Wilson WD, Poon GM (2014) Mechanistic heterogeneity in site recognition by the structurally homologous DNA-binding domains of the ETS family transcription factors Ets-1 and PU.1. J Biol Chem 289(31):21605–21616. https://doi.org/10.1074/jbc.M114.575340
Wang J, Malecka A, Trøen G, Delabie J (2015) Comprehensive genome-wide transcription factor analysis reveals that a combination of high affinity and low affinity DNA binding is needed for human gene regulation. BMC Genomics 16(7):S12. https://doi.org/10.1186/1471-2164-16-S7-S12
Wei GH, Badis G, Berger MF, Kivioja T, Palin K, Enge M, Bonke M, Jolma A, Varjosalo M, Gehrke AR, Yan J, Talukder S, Turunen M, Taipale M, Stunnenberg HG, Ukkonen E, Hughes TR, Bulyk ML, Taipale J (2010) Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo. EMBO J 29(13):2147–2160. https://doi.org/10.1038/emboj.2010.106
Weikum ER, Knuesel MT, Ortlund EA, Yamamoto KR (2017) Glucocorticoid receptor control of transcription: precision and plasticity via allostery. Nat Rev Mol Cell Biol 18(3):159–174. https://doi.org/10.1038/nrm.2016.152
Weingarten-Gabbay S, Segal E (2014) The grammar of transcriptional regulation. Hum Genet 133(6):701–711. https://doi.org/10.1007/s00439-013-1413-1
Wheeler RJ, Hyman AA (2018) Controlling compartmentalization by non-membrane-bound organelles. Philos Trans R Soc Lond Ser B Biol Sci 373(1747). https://doi.org/10.1098/rstb.2017.0193
Willenbrock H, Ussery DW (2004) Chromatin architecture and gene expression in Escherichia coli. Genome Biol 5(12):252. https://doi.org/10.1186/gb-2004-5-12-252
Witzany G (2017) Two genetic codes: repetitive syntax for active non-coding RNAs; non-repetitive syntax for the DNA archives. Commun Integr Biol 10(2):e1297352. https://doi.org/10.1080/19420889.2017.1297352
Wlodawer A, Minor W, Dauter Z, Jaskolski M (2008) Protein crystallography for non-crystallographers, or how to get the best (but not more) from published macromolecular structures. FEBS J 275(1):1–21. https://doi.org/10.1111/j.1742-4658.2007.06178.x
Xhani S, Esaki S, Huang K, Erlitzki N, Poon GM (2017) Distinct roles for interfacial hydration in site-specific DNA recognition by ETS-family transcription factors. J Phys Chem B 121(13):2748–2758. https://doi.org/10.1021/acs.jpcb.7b00325
Xhani S, Lee S, Kim HM, Wang S, Esaki S, Ha VLT, Khanezarrin M, Fernandez GL, Albrecht AV, Aramini JM, Germann MW, Poon GMK (2020) Intrinsic disorder controls two functionally distinct dimers of the master transcription factor PU.1. Sci Adv 6(8):eaay3178. https://doi.org/10.1126/sciadv.aay3178
Zhou Z, Giles KE, Felsenfeld G (2019) DNA.RNA triple helix formation can function as a cis-acting regulatory mechanism at the human beta-globin locus. Proc Natl Acad Sci U S A 116(13):6130–6139. https://doi.org/10.1073/pnas.1900107116
Zhu L, Brangwynne CP (2015) Nuclear bodies: the emerging biophysics of nucleoplasmic phases. Curr Opin Cell Biol 34:23–30. https://doi.org/10.1016/j.ceb.2015.04.003
Zuo Z, Stormo GD (2014) High-resolution specificity from DNA sequencing highlights alternative modes of Lac repressor binding. Genetics 198(3):1329–1343. https://doi.org/10.1534/genetics.114.170100
Zuo Z, Chang Y, Stormo GD (2015) A quantitative understanding of lac repressor's binding specificity and flexibility. Quant Biol 3(2):69–80. https://doi.org/10.1007/s40484-015-0044-z
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G.M.K.P is supported by NSF grant MCB 2028902 and NIH grants GM137160 and HL155178.
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Poon, G.M.K. (2021). The Non-continuum Nature of Eukaryotic Transcriptional Regulation. In: Atassi, M.Z. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 1371. Springer, Cham. https://doi.org/10.1007/5584_2021_618
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