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Gene Regulation in and out of Equilibrium
- Felix Wong1,2, and Jeremy Gunawardena3
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View Affiliations Hide AffiliationsAffiliations: 1Institute for Medical Engineering & Science, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA 2Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA 3Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA; email: [email protected]
- Vol. 49:199-226 (Volume publication date May 2020) https://doi.org/10.1146/annurev-biophys-121219-081542
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Copyright © 2020 by Annual Reviews. All rights reserved
Abstract
Determining whether and how a gene is transcribed are two of the central processes of life. The conceptual basis for understanding such gene regulation arose from pioneering biophysical studies in eubacteria. However, eukaryotic genomes exhibit vastly greater complexity, which raises questions not addressed by this bacterial paradigm. First, how is information integrated from many widely separated binding sites to determine how a gene is transcribed? Second, does the presence of multiple energy-expending mechanisms, which are absent from eubacterial genomes, indicate that eukaryotes are capable of improved forms of genetic information processing? An updated biophysical foundation is needed to answer such questions. We describe the linear framework, a graph-based approach to Markov processes, and show that it can accommodate many previous studies in the field. Under the assumption of thermodynamic equilibrium, we introduce a language of higher-order cooperativities and show how it can rigorously quantify gene regulatory properties suggested by experiment. We point out that fundamental limits to information processing arise at thermodynamic equilibrium and can only be bypassed through energy expenditure. Finally, we outline some of the mathematical challenges that must be overcome to construct an improved biophysical understanding of gene regulation.
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Literature Cited
-
1.Ackers GK, Johnson AD, Shea MA 1982. Quantitative model for gene regulation by lambda phage repressor. PNAS 791129–33Influential early use of equilibrium statistical mechanics for analyzing gene regulation.
-
2.Ahsendorf T, Wong F, Eils R, Gunawardena J 2014. A framework for modelling gene regulation which accommodates non-equilibrium mechanisms. BMC Biol. 12102
-
3.Allen BL, Taatjes DJ 2015. The Mediator complex: a central integrator of transcription. Nat. Rev. Mol. Cell Biol. 16155–66
-
4.Anderson E, Hill RE 2014. Long-range regulation of the sonic hedgehog gene. Curr. Opin. Genet. Dev. 2754–59
-
5.Anderson E, Peluso S, Lettice LA, Hill RE 2012. Human limb abnormalities caused by disruption of hedgehog signaling. Trends Genet. 28364–73
-
6.Arnosti DN, Barolo S, Levine M, Small S 1996. The eve stripe 2 enhancer employs multiple modes of transcriptional synergy. Development 122205–14
-
7.Arnosti DN, Kulkarni MM 2005. Transcriptional enhancers: intelligent enhanceosomes or flexible billboards?. J. Cell Biochem. 94890–98
-
8.Bailey SR, Maus MV 2019. Gene editing for immune cell therapies. Nat. Biotechnol. 371425–43
-
9.Battle C, Broedersz CP, Fakhri N, Geyer VF, Howard J 2016. Broken detailed balance at mesoscopic scales in active biological systems. Science 352604–7
-
10.Berry S, Dean C, Howard M 2017. Slow chromatin dynamics allow Polycomb target genes to filter fluctuations in transcription factor activity. Cell Syst. 4445–57
-
11.Biddle JW, Gunawardena J 2019. Reversal symmetries for cyclic paths away from thermodynamic equilibrium. arXiv:1910.03735 [cond-mat.stat-mech]
-
12.Biddle JW, Nguyen M, Gunawardena J 2019. Negative reciprocity, not ordered assembly, underlies the interaction of Sox2 and Oct4 on DNA. eLife 8e410172018
-
13.Bintu L, Buchler NE, Garcia HG, Gerland U, Hwa T 2005. Transcriptional regulation by the numbers: applications. Curr. Opin. Gen. Dev. 15125–35Influential review of the thermodynamic formalism.
-
14.Bintu L, Buchler NE, Garcia HG, Gerland U, Hwa T 2005. Transcriptional regulation by the numbers: models. Curr. Opin. Gen. Dev. 15116–24
-
15.Bintu L, Yong J, Antebi YE, McCue K, Kazuki Y 2016. Dynamics of epigenetic regulation at the single-cell level. Science 351720–24
-
16.Boeger H, Griesenbeck J, Kornberg RD 2008. Nucleosome retention and the stochastic nature of promoter chromatin remodeling for transcription. Cell 133716–26Early analysis of nonequilibrium regulatory behavior in yeast.
-
17.Bothma JP, Garcia HG, Ng S, Perry MW, Gregor T, Levine M 2015. Enhancer additivity and non-additivity are determined by enhancer strength in the Drosophila embryo. eLife 4e07956
-
18.Box GEP 1976. Science and statistics. J. Am. Stat. Assoc. 71791–99
-
19.Brewster RC, Weinert FM, Garcia HG, Song D, Rydenfelt M, Phillips R 2014. The transcription factor titration effect dictates level of gene expression. Cell 1561313–23
-
20.Brivanlou AH, Darnell JE Jr 2002. Signal transduction and the control of gene expression. Science 295813–18
-
21.Brown CR, Boeger H 2014. Nucleosomal promoter variation gene expression noise. PNAS 11117893–98
-
22.Brown CR, Mao C, Falkovskaia E, Jurica MS, Boeger H 2013. Linking stochastic fluctuations in chromatin structure and gene expression. PLOS Biol. 11e1001621
-
23.Buffry AD, Mendes CC, McGregor AP 2016. The functionality and evolution of eukaryotic transcriptional enhancers. Adv. Genet. 96143–206
-
24.Cannavò E, Khoueiry P, Garfield DA, Geeleher P, Zichner T 2016. Shadow enhancers are pervasive features of developmental regulatory networks. Curr. Biol. 2638–51
-
25.Carey M 1998. The enhanceosome and transcriptional synergy. Cell 925–8
-
26.Carey M, Lin YS, Green MR, Ptashne M 1990. A mechanism for synergistic activation of a mammalian gene by GAL4 derivatives. Nature 345361–64Evidence for HOC of high order between TFs and RNA polymerase.
-
27.Cavalli G, Misteli T 2013. Functional implications of genome topology. Nat. Struct. Mol. Biol. 20290–99
-
28.Chung FRK 1997. Spectral Graph Theory Providence, RI: Am. Math. Soc.
-
29.Cohen M, Page KM, Perez-Carrasco R, Barnes CP, Briscoe J 2014. A theoretical framework for the regulation of Shh morphogen-controlled gene expression. Development 1413868–78
-
30.Coleman RA, Liu Z, Darzacq X, Tjian R, Singer RH, Lionnet T 2015. Imaging transcription: past, present, and future. Cold Spring Harb. Symp. Quant. Biol. 801–8
-
31.Coulon A, Chow CC, Singer RH, Larson DR 2013. Eukaryotic transcriptional dynamics: from single molecules to cell populations. Nat. Rev. Genet. 14572–84Highlights the significance of nonequilibrium behavior.
-
32.Cremer T, Cremer M, Cremer C 2018. The 4D nucleome: genome compartmentalization in an evolutionary context. Biochemistry 83313–25
-
33.Crocker J, Abe N, Rinaldi L, McGregor AP, Frankel N 2015. Low affinity binding site clusters confer Hox specificity and regulatory robustness. Cell 160191–203
-
34.Culyba MJ 2019. Ordering up gene expression by slowing down transcription factor binding kinetics. Curr. Genet. 65401–6
-
35.Culyba MJ, Kubiak JM, Mo CY, Goulian M, Kohli RM 2018. Non-equilibrium repressor binding kinetics link DNA damage dose to transcriptional timing within the SOS gene network. PLOS Genet. 14e100740
-
36.Dangkulwanich M, Ishibashi T, Bintu L, Bustamante C 2014. Molecular mechanisms of transcription through single-molecule experiments. Chem. Rev. 1143203–23
-
37.Dasgupta T, Croll DH, Owen JA, Vander Heiden MG, Locasale JW 2014. A fundamental trade off in covalent switching and its circumvention by enzyme bifunctionality in glucose homeostasis. J. Biol. Chem. 28913010–25
-
38.Day JJ, Sweatt JD 2011. Epigenetic mechanisms in cognition. Neuron 11813–29
-
39.de Laat W, Duboule D 2013. Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502499–506
-
40.de Mendoza A, Sebé-Pedrós A, Šestak MS, Matejić M, Torruellaa G 2013. Transcription factor evolution in eukaryotes and the assembly of the regulatory toolkit in multicellular lineages. PNAS 110e4858–66
-
41.Dillon SC, Dorman CJ 2010. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat. Rev. Microbiol. 8185–95
-
42.Dodd IB, Micheelsen MA, Sneppen K, Thon G 2007. Theoretical analysis of epigenetic cell memory by nucleosome modification. Cell 129813–22
-
43.Dodd IB, Shearwin KE, Perkins AJ, Burr T, Hochschild A, Egan JB 2004. Cooperativity in long-range gene regulation by the λ CI repressor. Genes Dev. 18344–54
-
44.Dodd IB, Shearwin KE, Sneppen K 2007. Modelling transcriptional interference and DNA looping in gene regulation. J. Mol. Biol. 3691200–13
-
45.Drewell RA, Nevarez MJ, Kurata JS, Winkler LN, Li L, Dresch JM 2014. Deciphering the combinatorial architecture of a Drosophila homeotic gene enhancer. Mech. Dev. 13168–77
-
46.Erceg J, Saunders TE, Girardot C, Devos DP, Hufnagel L, Furlong EE 2014. Subtle changes in motif positioning cause tissue-specific effects on robustness of an enhancers activity. PLOS Genet. 10e1004060
-
47.Estrada J, Wong F, DePace A, Gunawardena J 2016. Information integration and energy expenditure in gene regulation. Cell 166234–44Introduces HOCs and establishes the Hopfield barrier for sharpness of gene expression.
-
48.Fakhouri WD, Ay A, Sayal R, Dresch J, Dayringer E, Arnosti DN 2010. Deciphering a transcriptional regulatory code: modeling short-range repression in the Drosophila embryo. Mol. Syst. Biol 6341
-
49.Farley EK, Olson KM, Zhang W, Brandt AJ, Rokhsar DS, Levine MS 2015. Suboptimization of developmental enhancers. Science 350325–28
-
50.Food Drug Assoc 2017. FDA approval brings first gene therapy to the United States News Release, Aug. 30. https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-gene-therapy-united-states
-
51.Frank TD, Carmody AM, Kholodenko BN 2012. Versatility of cooperative transcriptional activation: a thermodynamical modeling analysis for greater-than-additive and less-than-additive effects. PLOS ONE 7e34439
-
52.Gertz J, Siggia ED, Cohen BA 2009. Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature 457215–18
-
53.Giorgetti L, Siggers T, Tiana G, Caprara G, Notarbartolo S 2010. Noncooperative interactions between transcription factors and clustered DNA binding sites enable graded transcriptional responses to environmental inputs. Mol. Cell 37418–28
-
54.Granek JA, Clarke ND 2005. Explicit equilibrium modeling of transcription-factor binding and gene regulation. Genome Biol. 6R87
-
55.Gray S, Szymanski P, Levine M 1994. Short-range repression permits multiple enhancers to function autonomously within a complex promoter. Genes Dev. 81829–38
-
56.Gunawardena J 2012. A linear framework for time-scale separation in nonlinear biochemical systems. PLOS ONE 7e36321
-
57.Gunawardena J 2012. Silicon dreams of cells into symbols. Nat. Biotechnol. 30838–40
-
58.Gunawardena J 2014. Models in biology: “accurate descriptions of our pathetic thinking.”. BMC Biol 1229
-
59.Gunawardena J 2014. Time-scale separation: Michaelis and Menten's old idea, still bearing fruit. FEBS J. 281473–88
-
60.Hager G, McNally JG, Misteli T 2009. Transcription dynamics. Mol. Cell 35741–53
-
61.Hammar P, Walldén M, Fange D, Persson F, Baltekin O 2014. Direct measurement of transcription factor dissociation excludes a simple operator occupancy model for gene regulation. Nat. Genet. 46405–8
-
62.He X, Samee MAH, Blatti C, Sinha S 2010. Thermodynamics-based models of transcriptional regulation by enhancers: the roles of synergistic activation, cooperative binding and short-range repression. PLOS Comput. Biol. 6e1000935Extensive analysis of Drosophila segmentation gene regulation using the thermodynamic formalism.
-
63.Herre M, Korb E 2019. The chromatin landscape of neuronal plasticity. Curr. Opin. Neurobiol. 5979–86
-
64.Herschlag D, Johnson FB 1993. Synergism in transcriptional activation: a kinetic view. Genes Dev. 7173–79
-
65.Herz HM 2016. Enhancer deregulation in cancer and other diseases. BioEssays 381003–15
-
66.Hill TL 1966. Studies in irreversible thermodynamics. IV. Diagrammatic representation of steady state fluxes for unimolecular systems. J. Theor. Biol. 10442–59
-
67.Holwerda S, de Laat W 2012. Chromatin loops, gene positioning, and gene expression. Front. Genet. 3217
-
68.Hong JW, Hendrix DA, Levine MS 2008. Shadow enhancers as a source of evolutionary novelty. Science 3211314
-
69.Hopfield JJ 1974. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. PNAS 714135–39Pioneering insights into the functional significance of energy expenditure.
-
70.Iarovaia OV, Minina EP, Sheval EV, Onichtchouk D, Dokudovskaya S 2019. Nucleolus: a central hub for nuclear functions. Trends Cell Biol. 29647–59
-
71.Janssens H, Hou S, Jaeger J, Kim AR, Myasnikova E 2006. Quantitative and predictive model of transcriptional control of the Drosophila melanogaster even skipped gene. Nat. Genet. 381159–65
-
72.Junion G, Spivakov M, Girardot C, Braun M, Gustafson H 2012. A transcription factor collective defines cardiac cell fate and reflects lineage history. Cell 148473–86
-
73.Keung AJ, Joung JK, Khalil AS, Collins JJ 2015. Chromatin regulation at the frontier of synthetic biology. Nat. Rev. Genet. 16159–71
-
74.Kim HD, O'Shea EK 2008. A quantitative model of transcription factor-activated gene expression. Nat. Struct. Mol. Biol. 151192–98Early analysis of nonequilibrium regulatory behavior in yeast.
-
75.Kouzarides T 2007. Chromatin modifications and their function. Cell 128693–705
-
76.Kvon EZ, Kazmar T, Stampfel G, Yáñez-Cuna JO, Pagani M 2014. Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature 51291–95
-
77.Kvon EZ, Stampfel G, Yáñez-Cuna JO, Dickson BJ, Stark A 2012. HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature. Genes Dev. 26908–13
-
78.Lam FH, Steger DJ, O'Shea EK 2008. Chromatin decouples promoter threshold from dynamic range. Nature 453246–50
-
79.Lanctôt C, Cheutin T, Cremer M, Cavalli G, Cremer T 2007. Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions. Nat. Rev. Genet. 8104–15
-
80.Latchman DS 2015.Gene Control New York: Garland Sci.
-
81.Lee TI, Young RA 2013. Transcriptional regulation and its misregulation in disease. Cell 1521237–51
-
82.Lelli KM, Slattery M, Mann RS 2012. Disentangling the many layers of eukaryotic transcriptional regulation. Annu. Rev. Genet. 4643–68
-
83.Levine M, Tjian R 2003. Transcription regulation and animal diversity. Nature 424147–51
-
84.Li C, Cesbron F, Oehler M, Brunner M, Höfer T 2018. Frequency modulation of transcriptional bursting enables sensitive and rapid gene regulation. Cell Syst. 6409–23.e11Impact of nonequilibrium irreversibility in the transcriptional cycle on sensitivity.
-
85.Lucas T, Tran H, Romero CAP, Guillou A, Fradin C 2018. 3 minutes to precisely measure morphogen concentration. PLOS Genet. 14e1007676
-
86.Ma J 2005. Crossing the line between activation and repression. Trends Genet. 2154–59
-
87.Maniatis T, Falvo JV, Kim TH, Kim TK, Lin CH 1998. Structure and function of the interferon-β enhanceosome. Cold Spring Harb. Symp. Quant. Biol. 63609–20
-
88.Miller JA, Widom J 2003. Collaborative competition mechanism for gene activation in vivo. Mol. Cell. Biol. 231623–32
-
89.Mirny L 2010. Nucleosome-mediated cooperativity between transcription factors. PNAS 10722534–39
-
90.Mirzaev I, Bortz DM 2015. Laplacian dynamics with synthesis and degradation. Bull. Math. Biol. 771013–45
-
91.Mirzaev I, Gunawardena J 2013. Laplacian dynamics on general graphs. Bull. Math. Biol. 752118–49
-
92.Müller-Hill B 1996. The Lac Operon: A Short History of a Genetic Paradigm Berlin: Walter de Gruyter
-
93.Nogales E, Louder RK, He Y 2017. Structural insights into the eukaryotic transcription initiation machinery. Annu. Rev. Biophys. 4659–83
-
94.Ostuni R, Piccolo V, Barozzi I, Polletti S, Termanini A 2013. Latent enhancers activated by stimulation in differentiated cells. Cell 152157–71
-
95.Panne D 2008. The enhanceosome. Curr. Opin. Struct. Biol. 18236–42
-
96.Papatsenko D, Levine MS 2008. Dual regulation by the Hunchback gradient in the Drosophila embryo. PNAS 1052901–6
-
97.Park J, Estrada J, Johnson G, Ricci-Tam C, Bragdon M 2019. Dissecting the sharp response of a canonical developmental enhancer reveals multiple sources of cooperativity. eLife 8e41266Builds on Reference 47 to give evidence for HOC and energy expenditure.
-
98.Paulsson J 2004. Summing up the noise in gene networks. Nature 427415–18
-
99.Peccoud J, Ycart B 1995. Markovian modelling of gene product synthesis. Theor. Popul. Biol. 48222–34
-
100.Peeters E, van Oeffelen L, Nidal M, Forterre P, Charlier D 2013. A thermodynamic model of the cooperative interaction between the archaeal transcription factor Ss-LrpB and its tripartite operator DNA. Gene 524330–40
-
101.Peng PC, Sammee MAH, Sinha S 2015. Incorporating chromatin accessibility data into sequence-to-expression modeling. Biophys. J. 1081057–67
-
102.Petit F, Sears KE, Ahituv N 2017. Limb development: a paradigm of gene regulation. Nat. Rev. Genet. 18245–58
-
103.Phillips R, Belliveau NM, Chure G, Garcia HG, Razo-Mejia M, Scholes C 2019. Figure 1 theory meets figure 2 experiments in the study of gene expression. Annu. Rev. Biophys 48121–63
-
104.Polach KJ, Widom J 1996. A model for the cooperative binding of eukaryotic regulatory proteins to nucleosomal target sites. J. Mol. Biol. 258800–12
-
105.Prabakaran S, Lippens G, Steen H, Gunawardena J 2012. Post-translational modification: nature's escape from genetic imprisonment and the basis for cellular information processing. Wiley Interdiscip. Rev. Syst. Biol. Med. 4565–83
-
106.Ptashne M 2004.A Genetic Switch: Phage Lambda Revisited Cold Spring Harbor, NY: Cold Spring Harb. Lab. Press. 3rd ed.
-
107.Ptashne M, Gann A 2002.Genes and Signals Cold Spring Harbor, NY: Cold Spring Harb. Lab. Press
-
108.Purvis J, Lahav G 2013. Encoding and decoding cellular information through signaling dynamics. Cell 152945–56
-
109.Raveh-Sadka T, Levo M, Segal E 2009. Incorporating nucleosomes into thermodynamic models of transcription regulation. Genome Res. 191480–96
-
110.Reinitz J, Hou S, Sharp DH 2003. Transcriptional control in Drosophila. Complexus 154–64
-
111.Richards EJ, Elgin SCR 2002. Epigenetic codes for heterochromatin formation and silencing: rounding up the usual suspects. Cell 108489–500
-
112.Rosenfeld N, Young JW, Alon U, Swain PS, Elowitz MB 2005. Gene regulation at the single-cell level. Science 3071962–65
-
113.Saiz L, Rubi JM, Vilar JMG 2005. Inferring the in vivo looping properties of DNA. PNAS 10217642–45
-
114.Saiz L, Vilar JMG 2008. Ab initio thermodynamic modeling of distal multisite transcription regulation. Nucleic Acids Res. 36726–31
-
115.Samee MAH, Lydiard-Martin T, Biette KM, Vincent BJ, Bragdon MD 2017. Quantitative measurement and thermodynamic modeling of fused enhancers support a two-tiered mechanism for interpreting regulatory DNA. Cell Rep. 21236–45
-
116.Sánchez A, Choubey S, Kondev J 2013. Regulation of noise in gene expression. Annu. Rev. Biophys. 42469–91
-
117.Sánchez A, Kondev J 2008. Transcriptional control of noise in gene expression. PNAS 1055081–86
-
118.Sanders TJ, Marshall CJ, Santangelo TJ 2019. The role of Archaeal chromatin in transcription. J. Mol. Biol. 4314103–15
-
119.Sayal R, Dresch JM, Pushel I, Taylor BR, Arnosti DN 2016. Quantitative perturbation-based analysis of gene expression predicts enhancer activity in early Drosophila embryo. eLife 5e08445
-
120.Schleif R 1992. DNA looping. Annu. Rev. Biochem. 61199–223
-
121.Schnakenberg J 1976. Network theory of microscopic and macroscopic behavior of master equation systems. Rev. Mod. Phys. 48571–86
-
122.Scholes C, DePace A, Sánchez A 2017. Combinatorial gene regulation through kinetic control of the transcription cycle. Cell Syst. 497–108
-
123.Segal E, Raveh-Sadka T, Schroeder M, Unnerstall U, Gaul U 2008. Predicting expression patterns from regulatory sequence in Drosophila segmentation. Nature 451535–40
-
124.Segal E, Widom J 2009. From DNA sequence to transcriptional behaviour: a quantitative approach. Nat. Rev. Genet. 10443–56
-
125.Shea MA, Ackers GK 1985. The O
R control system of bacteriophage lambda: a physical-chemical model for gene regulation. J. Mol. Biol. 181211–30 -
126.Sherman MS, Cohen BA 2012. Thermodynamic state ensemble models of cis-regulation. PLOS Comput. Biol. 8e1002407
-
127.Small S, Blair A, Levine M 1992. Regulation of even-skipped stripe 2 in the Drosophila embryo. EMBO J. 114047–57
-
128.Spitz F, Furlong EEM 2012. Transcription factors: from enhancer binding to developmental control. Nat. Rev. Genet. 13613–26
-
129.Staller MV, Vincent BJ, Bragdon MDJ, Lydiard-Martin T, Wunderlich Z 2015. Shadow enhancers enable hunchback bifunctionality in the Drosophila embryo. PNAS 112785–90
-
130.Stewart AJ, Hannenhalli S, Plotkin JB 2012. Why transcription factor binding sites are ten nucleotides long. Genetics 192973–85
-
131.Struhl K, Segal E 2013. Determinants of nucleosome positioning. Nat. Struct. Mol. Biol. 20267–73
-
132.Talbert PB, Meers MP, Henikoff S 2019. Old cogs, new tricks: the evolution of gene expression in a chromatin context. Nat. Rev. Genet. 20283–97
-
133.Tran H, Desponds J, Romero CAP, Coppey M, Fradin C 2018. Precision in a rush: trade-offs between reproducibility and steepness of the hunchback expression pattern. PLOS Comp. Biol. 14e1006513
-
134.Tycko J, Van MV, Elowitz MB, Bintu L 2017. Advancing towards a global mammalian gene regulation model through single-cell analysis and synthetic biology. Curr. Opin. Biomed. Eng. 4174–93
-
135.van Steensel B, Furlong EEM 2019. The role of transcription in shaping the spatial organization of the genome. Nat. Rev. Mol. Cell Biol. 20327–37
-
136.Vashee S, Melcher K, Ding WV, Albert S, Johnston SA, Kodadek T 1998. Evidence for two modes of cooperative DNA binding in vivo that do not involve direct protein–protein interactions. Curr. Biol. 8452–58
-
137.Vermunt MW, Zhang D, Blobel GB 2019. The interdependence of gene-regulatory elements and the 3D genome. J. Cell Biol. 21812–26
-
138.Vilar JMG, Saiz L 2013. Systems biophysics of gene expression. Biophys. J. 1042574–85
-
139.von Hippel PH 2007. From “simple” DNA-protein interactions to the macromolecular machines of gene expression. Annu. Rev. Biophys. Biomol. Struct. 3679–105
-
140.von Hippel PH, Revzin A, Gross CA, Wang AC 1974. Non-specific DNA binding of genome regulating proteins as a biological control mechanism: 1. The lac operon: equilibrium aspects. PNAS 714808–12
-
141.Voss TC, Hager GL 2014. Dynamic regulation of transcriptional states by chromatin and transcription factors. Nat. Rev. Genet. 1569–81
-
142.Voss TC, Schiltz RL, Sung MH, Yen PM, Stamatoyannopoulos JA 2011. Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell 146544–54
-
143.Wang J, Ellwood K, Lehman A, Carey MF, She ZS 1999. A mathematical model for synergistic eukaryotic gene activation. J. Mol. Biol. 286315–25
-
144.Wong F, Amir A, Gunawardena J 2018. Energy-speed-accuracy relation in complex networks for biological discrimination. Phys. Rev. E 98012420
-
145.Wong F, Dutta A, Chowdhury D, Gunawardena J 2018. Structural conditions on complex networks for the Michaelis-Menten input-output response. PNAS 1159738–43
-
146.Wray GA, Hahn MW, Abouheif E, Balhoff JP, Pizer M 2003. The evolution of transcriptional regulation in eukaryotes. Mol. Biol. Evol. 201377–419
-
147.Zhang Z, Wippo CJ, Wal M, Ward E, Korber P, Pugh BF 2011. A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome. Science 332977–80
-
148.Zinzen RP, Senger K, Levine M, Papatsenko D 2006. Computational models for neurogenic gene expression in the Drosophila embryo. Curr. Biol. 161358–65
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