What have single-molecule studies taught us about gene expression?

Genes and Development

Volumn 30, Issue 16, 2016, Pages 1796-1810

  Chen, Huimin ^a   Larson, Daniel R ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Fluorescence; Single molecule; Splicing; Transcription

Indexed keywords

DNA; RNA; RNA POLYMERASE; SMALL NUCLEAR RIBONUCLEOPROTEIN; TRANSCRIPTION FACTOR; DNA DIRECTED RNA POLYMERASE;

ALTERNATIVE RNA SPLICING; BACTERIUM; CELL NUCLEUS; CYTOARCHITECTURE; EUKARYOTIC CELL; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENETIC VARIABILITY; HUMAN; IN VITRO STUDY; MOLECULAR BIOLOGY; MOLECULAR DYNAMICS; MOLECULE; NONHUMAN; PRIORITY JOURNAL; REVIEW; RNA PROCESSING; RNA SYNTHESIS; SINGLE CELL ANALYSIS; TRANSCRIPTION ELONGATION; TRANSCRIPTION INITIATION; ANIMAL; GENETIC PROCEDURES; METABOLISM; RNA SPLICING; STANDARDS; TRANSLATION ELONGATION; TRENDS;

ANIMALS; CELL NUCLEUS; DNA-DIRECTED RNA POLYMERASES; GENE EXPRESSION REGULATION; GENETIC TECHNIQUES; HUMANS; PEPTIDE CHAIN ELONGATION, TRANSLATIONAL; RNA SPLICING; TRANSCRIPTION FACTORS;

EID: 84986921883     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.281725.116     Document Type: Review

References (153)

1. Abbondanzieri EA, Greenleaf WJ, Shaevitz JW, Landick R, Block SM. 2005. Direct observation of base-pair stepping by RNA polymerase. Nature 438: 460-465.
2. Abelson J, Blanco M, Ditzler MA, Fuller F, Aravamudhan P, Wood M, Villa T, Ryan DE, Pleiss JA, Maeder C, et al. 2010. Conformational dynamics of single pre-mRNA molecules during in vitro splicing. Nat Struct Mol Biol 17: 504-512.
3. Adelman K, La Porta A, Santangelo TJ, Lis JT, Roberts JW, Wang MD. 2002. Single molecule analysis of RNA polymerase elongation reveals uniform kinetic behavior. Proc Natl Acad Sci 99: 13538-13543.
4. Agafonov DE, Kastner B, Dybkov O, Hofele RV, Liu WT, Urlaub H, Luhrmann R, Stark H. 2016. Molecular architecture of the human U4/U6.U5 tri-snRNP. Science 351: 1416-1420.
5. Bartman CR, Hsu SC, Hsiung CC, Raj A, Blobel GA. 2016. Enhancer regulation of transcriptional bursting parameters revealed by forced chromatin looping. Mol Cell 62: 237-247.
6. Beliveau BJ, Boettiger AN, Avendaño MS, Jungmann R, McCole RB, Joyce EF, Kim-Kiselak C, Bantignies F, Fonseka CY, Erceg J, et al. 2015. Single-molecule super-resolution imaging of chromosomes and in situ haplotype visualization using Oligopaint FISH probes. Nat Commun 6: 7147.
7. Berg OG, Blomeerg C. 1976. Association kinetics with coupled diffusional flows: special application to the Lac repressor-operator system. Biophys Chem 4: 367-381.
8. Berg OG, Winter RB, von Hippel PH. 1981. Diffusion-driven mechanisms of protein translocation on nucleic acids. 1. Models and theory. Biochemistry 20: 6929-6948.
9. Berget SM, Moore C, Sharp PA. 1977. Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Rev Med Virol 10:356-362.
10. Bintu L, Kopaczynska M, Hodges C, Lubkowska L, Kashlev M, Bustamante C. 2011. The elongation rate of RNA polymerase determines the fate of transcribed nucleosomes. Nat Struct Mol Biol 18: 1394-1399.
11. Bintu L, Ishibashi T, Dangkulwanich M, Wu YY, Lubkowska L, Kashlev M, Bustamante C. 2012. Nucleosomal elements that control the topography of the barrier to transcription. Cell 151: 738-749.
12. Blake WJ, Balazsi G, Kohanski MA, Isaacs FJ, Murphy KF, Kuang Y, Cantor CR, Walt DR, Collins JJ. 2006. Phenotypic consequences of promoter-mediated transcriptional noise. Mol Cell 24: 853-865.
13. Boettiger AN, Bintu B, Moffitt JR, Wang S, Beliveau BJ, Fudenberg G, Imakaev M, Mirny LA, Wu C, Zhuang X. 2016. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature 529: 418-422.
14. Bonnet I, Biebricher A, Porte PL, Loverdo C, Benichou O, Voituriez R, Escude C, Wende W, Pingoud A, Desbiolles P. 2008. Sliding and jumping of single EcoRV restriction enzymes on non-cognate DNA. Nucleic Acids Res 36: 4118-4127.
15. Braberg H, Jin H, Moehle EA, Chan YA, Wang S, Shales M, Benschop JJ, Morris JH, Qiu C, Hu F, et al. 2013. From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II. Cell 154: 775-788.
16. Brieba LG, Sousa R. 2001. T7 promoter release mediated by DNA scrunching. EMBO J 20: 6826-6835.
17. Brody Y, Neufeld N, Bieberstein N, Causse SZ, Böhnlein E-M, Neugebauer KM, Darzacq X, Shav-Tal Y. 2011. The in vivo kinetics of RNA polymerase II elongation during co-transcriptional splicing. PLoS Biol 9: e1000573.
18. Brown CR, Mao C, Falkovskaia E, Jurica MS, Boeger H. 2013. Linking stochastic fluctuations in chromatin structure and gene expression. PLoS Biol 11: e1001621.
19. Carpousis AJ, Gralla JD. 1985. Interaction of RNA polymerase with lacUV5 promoter DNA during mRNA initiation and elongation. J Mol Biol 183: 165-177.
20. Chen B, Gilbert LA, Cimini BA, Schnitzbauer J, Zhang W, Li GW, Park J, Blackburn EH, Weissman JS, Qi LS, et al. 2013. Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system. Cell 155: 1479-1491.
21. Chen J, Zhang Z, Li L, Chen BC, Revyakin A, Hajj B, Legant W, Dahan M, Lionnet T, Betzig E, et al. 2014. Single-molecule dynamics of enhanceosome assembly in embryonic stem cells. Cell 156: 1274-1285.
22. Cho W, Jayanth N, English BP, Inoue T, Andrews JO, Cissé I. 2016. RNA polymerase II cluster dynamics predict mRNA output in living cells. Elife 5: e13617.
23. Choi PJ, Cai L, Frieda K, Xie XS. 2008. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science 322: 442-446.
24. Chong S, Chen C, Ge H, Xie XS. 2014. Mechanism of transcriptional bursting in bacteria. Cell 158: 314-326.
25. Chubb JR, Trcek T, Shenoy SM, Singer RH. 2006. Transcriptional pulsing of a developmental gene. Curr Biol 16: 1018-1025.
26. Cisse II, Izeddin I, Causse SZ, Boudarene L, Senecal A, Muresan L, Dugast-Darzacq C, Hajj B. 2013. Real-time dynamics of RNA polymerase II clustering in live human cells. Science 245: 664-667.
27. Cook PR. 1999. The organization of replication and transcription. Science 284: 1790-1795.
28. Corrigan AM, Tunnacliffe E, Cannon D, Chubb JR. 2016. A continuum model of transcriptional bursting. Elife 5: e13051.
29. Coulon A, Chow CC, Singer RH, Larson DR. 2013. Eukaryotic transcriptional dynamics: from single molecules to cell populations. Nat Rev Genet 14: 572-584.
30. Coulon A, Ferguson ML, de Turris V, Palangat M, Chow CC, Larson DR. 2014. Kinetic competition during the transcription cycle results in stochastic RNA processing. Elife 3: e03939.
31. Crawford DJ, Hoskins AA, Friedman LJ, Gelles J, Moore MJ. 2008. Visualizing the splicing of single pre-mRNA molecules in whole cell extract. RNA 14: 170-179.
32. Crawford DJ, Hoskins AA, Friedman LJ, Gelles J, Moore MJ. 2013. Single-molecule colocalization FRET evidence that spliceosome activation precedes stable approach of 5′ splice site and branch site. Proc Natl Acad Sci 110: 6783-6788.
33. Darzacq X, Shav-Tal Y, de Turris V, Brody Y, Shenoy SM, Phair RD, Singer RH. 2007. In vivo dynamics of RNA polymerase II transcription. Nat Struct Mol Biol 14: 796-806.
34. Davenport RJ, Wuite GJ, Landick R, Bustamante C. 2000. Singlemolecule study of transcriptional pausing and arrest by E. coli RNA polymerase. Science 287: 2497-2500.
35. de la Mata M, Alonso CR, Kadener S, Fededa JP, Blaustein M, Pelisch F, Cramer P, Bentley D, Kornblihtt AR. 2003. A slow RNA polymerase II affects alternative splicing in vivo. Mol Cell 12: 525-532.
36. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B. 2012. Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485: 376-380.
37. Elf J, Li G-W, Xie XS. 2007. Probing transcription factor dynamics at the single-molecule level in a living cell. Science 316: 1191-1194.
38. Fazal FM, Meng CA, Murakami K, Kornberg RD, Block SM. 2015. Real-time observation of the initiation of RNA polymerase II transcription. Nature 525: 274-277.
39. Featherstone K, Hey K, Momiji H, McNamara AV, Patist AL, Woodburn J, Spiller DG, Christian HC, McNeilly AS, Mullins JJ, et al. 2016. Spatially coordinated dynamic gene transcription in living pituitary tissue. Elife 5: 1-25.
40. Femino AM, Fay FS, Fogarty K, Singer RH. 1998. Visualization of single RNA transcripts in situ. Science 280: 585-590.
41. Fong N, Kim H, Zhou Y, Ji X, Qiu J, Saldi T, Diener K, Jones K, Fu XD, Bentley DL. 2014. Pre-mRNA splicing is facilitated by an optimal RNA polymerase II elongation rate. Genes Dev 28: 2663-2676.
42. Friedman LJ, Gelles J. 2012. Mechanism of transcription initiation at an activator-dependent promoter defined by singlemolecule observation. Cell 148: 679-689.
43. Friedman LJ, Mumm JP, Gelles J. 2013. RNA polymerase approaches its promoter without long-range sliding along DNA. Proc Natl Acad Sci 110: 9740-9745.
44. Fukaya T, Lim B, Levine M. 2016. Enhancer control of transcriptional bursting. Cell 166: 358-368.
45. Galburt EA, Grill SW, Wiedmann A, Lubkowska L, Choy J, Nogales E, Kashlev M, Bustamante C. 2007. Backtracking determines the force sensitivity of RNAP II in a factor-dependent manner. Nature 446: 820-823.
46. Gandhi SJ, Zenklusen D, Lionnet T, Singer RH. 2011. Transcription of functionally related constitutive genes is not coordinated. Nat Struct Mol Biol 18: 27-34.
47. Garcia HG, Tikhonov M, Lin A, Gregor T. 2013. Quantitative imaging of transcription in living Drosophila embryos links polymerase activity to patterning. Curr Biol 23: 2140-2145.
48. Gebhardt JCM, Suter DM, Roy R, Zhao ZW, Chapman AR, Basu S, Maniatis T, Xie XS. 2013. Single-molecule imaging of transcription factor binding to DNA in live mammalian cells. Nat Methods 10: 421-426.
49. Golding I, Paulsson J, Zawilski SM, Cox EC. 2005. Real-time kinetics of gene activity in individual bacteria. Cell 123: 1025-1036.
50. Greenleaf WJ, Woodside MT, Block SM. 2007. High-resolution, single-molecule measurements of biomolecular motion. Annu Rev Biophys Biomol Struct 36: 171-190.
51. Grimm JB, English BP, Chen J, Slaughter JP, Zhang Z, Revyakin A, Patel R, Macklin JJ, Normanno D, Singer RH, et al. 2015. A general method to improve fluorophores for live-cell and singlemolecule microscopy. Nat Methods 12: 4-7.
52. Guo Z, Karunatilaka KS, Rueda D. 2009. Single-molecule analysis of protein-free U2-U6 snRNAs. Nat Struct Mol Biol 16: 1154-1159.
53. Hammar P, Leroy P, Mahmutovic A, Marklund EG, Berg OG, Elf J. 2012. The lac repressor displays facilitated diffusion in living cells. Science 336: 1595-1598.
54. Hawley DK, Roeder RG. 1987. Functional steps in transcription initiation and reinitiation from the major late promoter in a HeLa nuclear extract. J Biol Chem 262: 3452-3461.
55. He Y, Yan C, Fang J, Inouye C, Tjian R, Ivanov I, Nogales E. 2016. Near-atomic resolution visualization of human transcription promoter opening. Nature 533: 1-21.
56. Hodges C, Bintu L, Lubkowska L, Kashlev M, Bustamante C. 2009. Nucleosomal fluctuations govern the transcription dynamics of RNA polymerase II. Science 325: 626-628.
57. Hornung G, Bar-Ziv R, Rosin D, Tokuriki N, Tawfik DS, Oren M, Barkai N. 2012. Noise-mean relationship in mutated promoters. Genome Res 22: 2409-2417.
58. Hoskins AA, Moore MJ. 2012. The spliceosome: a flexible, reversible macromolecular machine. Trends Biochem Sci 37: 179-188.
59. Hoskins AA, Friedman LJ, Gallagher SS, Crawford DJ, Anderson EG, Wombacher R, Ramirez N, Cornish VW, Gelles J, Moore MJ. 2011. Ordered and dynamic assembly of single spliceosomes. Science 331: 1289-1296.
60. Huang B, Babcock H, Zhuang X. 2010. Breaking the diffraction barrier: super-resolution imaging of cells. Cell 143: 1047-1058.
61. Ishibashi T, Dangkulwanich M, Coello Y, Lionberger TA, Lubkowska L, Ponticelli AS, Kashlev M, Bustamante C. 2014. Transcription factors IIS and IIF enhance transcription efficiency by differentially modifying RNA polymerase pausing dynamics. Proc Natl Acad Sci 111: 3419-3424.
62. Izeddin I, Récamier V, Bosanac L, Cissé II, Boudarene L, Dugast-Darzacq C, Proux F, Bénichou O, Voituriez R, Bensaude O, et al. 2014. Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus. Elife 2014: 1-27.
63. Janicki SM, Tsukamoto T, Salghetti SE, Tansey WP, Sachidanandam R, Prasanth KV, Ried T, Shav-Tal Y, Bertrand E, Singer RH, et al. 2004. From silencing to gene expression: real-time analysis in single cells. Cell 116: 683-698.
64. Jonkers I, Lis JT. 2015. Getting up to speed with transcription elongation by RNA polymerase II. Nat Rev Mol Cell Biol 16: 167-177.
65. Joo C, Balci H, Ishitsuka Y, Buranachai C, Ha T. 2008. Advances in single-molecule fluorescence methods for molecular biology. Annu Rev Biochem 77: 51-76.
66. Kapanidis AN, Margeat E, Ho SO, Kortkhonjia E, Weiss S, Ebright RH. 2006. Initial transcription by RNA polymerase proceedsthrough a DNA-scrunching mechanism. Science 314: 1144-1147.
67. Karpova TS, Kim MJ, Spriet C, Nalley K, Stasevich TJ, Kherrouche Z, Heliot L, Mcnally JG. 2008. Concurrent fast and slow cycling. Science 319: 466-469.
68. Kieffer-Kwon KR, Tang Z, Mathe E, Qian J, Sung MH, Li G, Resch W, Baek S, Pruett N, Grontved L, et al. 2013. Interactome maps of mouse gene regulatory domains reveal basic principles of transcriptional regulation. Cell 155: 1507-1520.
69. Ko MS, Nakauchi H, Takahashi N. 1990. The dose-dependence of glucocorticoid-inducible gene expression results from the change in the number of transcriptionally active templates. EMBO J 9: 2835-2842.
70. Krishnan R, Blanco MR, Kahlscheuer ML, Abelson J, Guthrie C, Walter NG. 2013. Biased Brownian ratcheting leads to premRNA remodeling and capture prior to first-step splicing. Nat Struct Mol Biol 20: 1450-1457.
71. Krummel B, Chamberlin MJ. 1989. RNA chain initiation by Escherichia coli RNA polymerase: structural transitions of the enzyme in early ternary complexes. Biochemistry 28: 7829-7842.
72. Landick R, Carey J, Yanofsky C. 1987. Detection of transcriptionpausing in vivo in the trp operon leader region. Proc Natl Acad Sci 84: 1507-1511.
73. Larson MH, Greenleaf WJ, Landick R, Block SM. 2008. Applied force reveals mechanistic and energetic details of transcription termination. Cell 132: 971-982.
74. Larson DR, Zenklusen D, Wu B, Chao JA, Singer RH. 2011. Realtime observation of transcription initiation and elongation on an endogenous yeast gene. Science 332: 275-278.
75. Larson DR, Fritzsch C, Sun L, Meng X, Lawrence DS, Singer RH. 2013. Direct observation of frequency modulated transcription in single cells using light activation. Elife 2: e00750.
76. Larson MH, Mooney RA, Peters JM, Windgassen T, Nayak D, Gross CA, Block SM, Greenleaf WJ, Landick R, Weissman JS. 2014. A pause sequence enriched at translation start sites drives transcription dynamics in vivo. Science 344: 1042-1047.
77. Lee DJ, Minchin SD, Busby SJW. 2012. Activating transcription in bacteria. Annu Rev Microbiol 66: 125-152.
78. Lenstra TL, Coulon A, Chow CC, Larson DR. 2015. Single-molecule imaging reveals a switch between spurious and functional ncRNA transcription. Mol Cell 60: 597-610.
79. Li GW, Xie XS. 2011. Central dogma at the single-molecule level in living cells. Nature 475: 308-315.
80. Li G, Ruan X, Auerbach RK, Sandhu KS, Zheng M, Wang P, Poh HM, Goh Y, Lim J, Zhang J, et al. 2012. Extensive promotercentered chromatin interactions provide a topological basis for transcription regulation. Cell 148: 84-98.
81. Lionnet T, Czaplinski K, Darzacq X, Shav-Tal Y, Wells AL, Chao JA, Park HY, de Turris V, Lopez-Jones M, Singer RH. 2011. A transgenic mouse for in vivo detection of endogenous labeled mRNA. Nat Methods 8: 165-170.
82. Little SC, Tikhonov M, Gregor T. 2013. Precise developmental gene expression arises from globally stochastic transcriptional activity. Cell 154: 789-800.
83. Liu Z, Legant WR, Chen B-C, Li L, Grimm JB, Lavis LD, Betzig E, Tjian R. 2014. 3D imaging of Sox2 enhancer clusters in embryonic stem cells. Elife 3: 1-29.
84. Liu Z, Lavis LD, Betzig E. 2015. Imaging live-cell dynamics and structure at the single-molecule level. Mol Cell 58: 644-659.
85. Lucas JS, Zhang Y, Dudko OK, Murre C. 2014. 3D trajectories adopted by coding and regulatory DNA elements: first-passage times for genomic interactions. Cell 158: 339-352.
86. Luo Y, North JA, Rose SD, Poirier MG. 2014. Nucleosomes accelerate transcription factor dissociation. Nucleic Acids Res 42: 3017-3027.
87. Ma J, Bai L, Wang MD. 2013. Transcription under torsion. Science 340: 1580-1583.
88. Martin RM, Rino J, Carvalho C, Kirchhausen T, Carmo-Fonseca M. 2013. Live-cell visualization of pre-mRNA splicing with single-molecule sensitivity. Cell Rep 4: 1144-1155.
89. Mazza D, Abernathy A, Golob N, Morisaki T, McNally JG. 2012. A benchmark for chromatin binding measurements in live cells. Nucleic Acids Res 40: 1-13.
90. McKnight SL, Miller OL Jr. 1979. Post-replicative nonribosomal transcription units in D. melanogaster embryos. Cell 17: 551-563.
91. Miller OL, Bakken A. 1972. Morphological studies of transcription. Acta Endocrinol 71: S155-S177.
92. Morisaki T, Müller WG, Golob N, Mazza D, McNally JG. 2014. Single-molecule analysis of transcription factor binding at transcription sites in live cells. Nat Commun 5: 4456.
93. Murakami K, Elmlund H, Kalisman N, Bushnell DA, Adams CM, Azubel M, Elmlund D, Levi-Kalisman Y, Liu X, Gibbons BJ, et al. 2013. Architecture of an RNA polymerase II transcription pre-initiation complex. Science 342: 123-8724.
94. Muramoto T, Müller I, Thomas G, Melvin A, Chubb JR. 2010. Methylation of H3K4 is required for inheritance of active transcriptional states. Curr Biol 20: 397-406.
95. Nagano T, Lubling Y, Stevens TJ, Schoenfelder S, Yaffe E, Dean W, Laue ED, Tanay A, Fraser P. 2013. Single-cell Hi-C reveals cell-to-cell variability in chromosome structure. Nature 502: 59-64.
96. Neher E, Sakmann B. 1976. Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260: 799-802.
97. Neuman KC, Abbondanzieri EA, Landick R, Gelles J, Block SM. 2003. Ubiquitous transcriptional pausing is independent of RNA polymerase backtracking. Cell 115: 437-447.
98. Newman JRS, Ghaemmaghami S, Ihmels J, Breslow DK, Noble M, DeRisi JL, Weissman JS. 2006. Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature 441: 840-846.
99. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, Servant N, Piolot T, van Berkum NL, Meisig J, Sedat J, et al. 2012. Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485: 381-385.
100. Normanno D, Boudarène L, Dugast-Darzacq C, Chen J, Richter C, Proux F, Bénichou O, Voituriez R, Darzacq X, Dahan M. 2015. Probing the target search of DNA-binding proteins inmammalian cells using TetR as model searcher. NatCommun 6: 7357.
101. Orphanides G, Weinberg D. 2002.Aunified theory of gene expression. Cell 108: 439-451.
102. Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, et al. 2004. Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36: 1065-1071.
103. Padovan-Merhar O, Nair GP, Biaesch AG, Mayer A, Scarfone S, Foley SW, Wu AR, Churchman LS, Singh A, Raj A. 2015. Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms. Mol Cell 58: 339-352.
104. Pal M, Ponticelli AS, Luse DS. 2005. The role of the transcription bubble and TFIIB in promoter clearance by RNA polymerase II. Mol Cell 19: 101-110.
105. Palangat M, Larson DR. 2012. Complexity of RNA polymerase II elongation dynamics. Biochim Biophys Acta 1819: 667-672.
106. Palangat M, Larson MH, Hu X, Gnatt A, Block SM, Landick R. 2012. Efficient reconstitution of transcription elongation complexes for single-molecule studies of eukaryotic RNA polymerase II. Transcription 3: 146-153.
107. Paulsson J. 2004. Summing up the noise in gene networks. Nature 427: 415-418.
108. Peccoud J, Ycart B. 1995. Markovian modeling of gene-product synthesis. Theor Popul Biol 48: 222-234.
109. Piston DW, Kremers G-J. 2007. Fluorescent protein FRET: the good, the bad and the ugly. Trends Biochem Sci 32: 407-414.
110. Raj A, Peskin CS, Tranchina D, Vargas DY, Tyagi S. 2006. Stochastic mRNA synthesis in mammalian cells. PLoS Biol 4: e309.
111. Revyakin A, Liu C, Ebright RH, Strick TR. 2006. Abortive initiation and productive initiation by RNA polymerase involve DNA scunching. Science 314: 1139-1143.
112. Revyakin A, Zhang Z, Coleman RA, Li Y, Inouye C, Lucas JK, Park S-R, Chu S, Tjian R. 2012. Transcription initiation by human RNA polymerase II visualized at single-molecule resolution. Genes Dev 26: 1691-1702.
113. Richter PH, Eigen M. 1974. Diffusion controlled reaction rates in spheroidal geometry. Biophys Chem 2: 255-263.
114. Riggs AD, Bourgeois S, Cohn M. 1970. The lac repressor-operator interaction. J Mol Biol 53: 401-417.
115. Robb NC, Cordes T, Hwang LC, Gryte K, Duchi D, Craggs TD, Santoso Y, Weiss S, Ebright RH, Kapanidis AN. 2013. The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection. J Mol Biol 425: 875-885.
116. Sainsbury S, Bernecky C, Cramer P. 2015. Structural basis of transcription initiation by RNA polymerase II. Nat Rev Mol Cell Biol 16: 129-143.
117. Schafer DA, Gelles J, Sheetz MP, Landick R. 1991. Transcription by single molecules of RNA polymerase observed by light microscopy. Nature 352: 444-448.
118. Schermelleh L, Heintzmann R, Leonhardt H. 2010. A guide to super-resolution fluorescence microscopy. J Cell Biol 190: 165-175.
119. Schmidt U, Basyuk E, Robert MC, Yoshida M, Villemin JP, Auboeuf D, Aitken S, Bertrand E. 2011. Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation. J Cell Biol 193: 819-829.
120. Schweikhard V, Meng C, Murakami K, Kaplan CD, Kornberg RD, Block SM. 2014. Transcription factors TFIIF and TFIIS promote transcript elongation by RNA polymerase II by synergistic and independent mechanisms. Proc Natl Acad Sci 111:6642-6647.
121. Semlow DR, Blanco MR, Walter NG, Staley JP. 2016. Spliceosomal DEAH-boxATPases remodel pre-mRNAto activate alternative splice sites. Cell 164: 985-998.
122. Shachar S, Voss TC, Pegoraro G, Sciascia N, Misteli T. 2015. Identification of gene positioning factors using high-throughput imaging mapping. Cell 162: 911-923.
123. Shaevitz JW, Abbondanzieri EA, Landick R, Block SM. 2003. Backtracking by single RNA polymerase molecules observed at near-base-pair resolution. Nature 426: 684-687.
124. Shahrezaei V, Swain PS. 2008. Analytical distributions for stochastic gene expression. ProcNatl Acad Sci 105: 17256-17261.
125. Shcherbakova I, Hoskins AA, Friedman LJ, Serebrov V, Correa IR Jr, Xu MQ, Gelles J, Moore MJ. 2013. Alternative spliceosome assembly pathways revealed by single-molecule fluorescence microscopy. Cell Rep 5: 151-165.
126. So L, Ghosh A, Zong C, Sepulveda LA, Segev R, Golding I. 2011. General properties of transcriptional time series in Escherichia coli. Nat Genet 43: 554-560.
127. Stevense M, Muramoto T, Müller I, Chubb JR. 2010. Digital nature of the immediate-early transcriptional response. Development 137: 579-584.
128. Stoeger T, Battich N, Pelkmans L. 2016. Passive noise filtering by cellular compartmentalization. Cell 164: 1151-1161.
129. Straney DC, Crothers DM. 1987. A stressed intermediate in the formation of stably initiated RNA chains at the Escherichia coli lac UV5 promoter. J Mol Biol 193: 267-278.
130. Studitsky VM, Clark DJ, Felsenfeld G. 1994. A histone octamer can step around a transcribing polymerase without leaving the template. Cell 76: 371-382.
131. Studitsky VM, Kassavetis GA, Geiduschek EP, Felsenfeld G. 1997. Mechanism of transcription through the nucleosome by eukaryotic RNA polymerase. Science 278: 1960-1963.
132. Swinstead EE, Miranda TB, Paakinaho V, Baek S, Goldstein I, Hawkins M, Karpova TS, Ball D, Mazza D, Lavis LD, et al. 2016. Steroid receptors reprogram FoxA1 occupancy through ynamic chromatin transitions. Cell 165: 593-605.
133. Tafvizi A, Huang F, Leith JS, Fersht AR, Mirny LA, van Oijen AM. 2008. Tumor suppressor p53 slides on DNA with low friction and high stability. Biophys J 95: L01-L03.
134. Therizols P, Illingworth RS, Courilleau C, Boyle S, Wood AJ, Bickmore WA. 2014. Chromatin decondensation is sufficient to alter nuclear organization in embryonic stem cells. Science 346: 1238-1242.
135. Tolic-Nørrelykke SF, Engh AM, Landick R, Gelles J. 2004. Diversity in the rates of transcript elongation by single RNA polymerase molecules. J Biol Chem 279: 3292-3299.
136. Trapnell C. 2015. Defining cell types and states with single-cell genomics. Genome Res 25: 1491-1498.
137. Vargas DY, Shah K, Batish M, Levandoski M, Sinha S, Marras SAE, Schedl P, Tyagi S. 2011. Single-molecule imaging of transcriptionally coupled and uncoupled splicing. Cell 147: 1054-1065.
138. Voss TC, Schiltz RL, Sung MH, Yen PM, Stamatoyannopoulos JA, Biddie SC, Johnson TA, Miranda TB, John S, Hager GL. 2011. Dynamic exchange at regulatory elements during chromatin remodeling underlies assisted loading mechanism. Cell 146: 544-554.
139. Wan R, Yan C, Bai R, Wang L, Huang M, Wong CC, Shi Y. 2016. The 3.8 A structure of the U4/U6.U5 tri-snRNP: insights into spliceosome assembly and catalysis. Science 351: 466-475.
140. Wang YM, Austin RH, Cox EC. 2006. Single molecule measurements of repressor protein 1D diffusion on DNA. Phys Rev Lett 97: 048-302.
141. Wang Y, Guo L, Golding I, Cox EC, Ong NP. 2009. Quantitative transcription factor binding kinetics at the single-molecule level. Biophys J 96: 609-620.
142. Wang F, Redding S, Finkelstein IJ, Gorman J, Reichman DR, Greene EC. 2013. The promoter-search mechanism of Escherichia coli RNA polymerase is dominated by three-dimensional diffusion. Nat Struct Mol Biol 20: 174-181.
143. White MR, Masuko M, Amet L, Elliott G, Braddock M, Kingsman AJ, Kingsman SM. 1995. Real-time analysis of the transcriptional regulation of HIV and hCMV promoters in single mammalian cells. J Cell Sci 108: 441-455.
144. White MD, Angiolini JF, Alvarez YD, Kaur G, Zhao ZW, Mocskos E, Bruno L, Bissiere S, Levi V, Plachta N. 2016. Long-lived binding of Sox2 to DNA predicts cell fate in the four-cell mouse embryo. Cell 165: 75-87.
145. Williamson I, Berlivet S, Eskeland R, Boyle S, Illingworth RS, Paquette D, Dostie J, Bickmore WA. 2014. Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization. Genes Dev 28: 2778-2791.
146. Winkelman JT, Vvedenskaya IO, Zhang Y, Zhang Y, Bird JG, Taylor DM, Gourse RL, Ebright RH, Nickels BE. 2016. Multiplexed protein-DNA cross-linking: scrunching in transcription start site selection. Science 351: 1090-1093.
147. Yan C, Hang J, Wan R, Huang M, Wong CC, Shi Y. 2015. Structure of a yeast spliceosome at 3.6-angstrom resolution. Science 349: 1182-1191.
148. Yin H, Artsimovitch I, Landick R, Gelles J. 1999. Nonequilibrium mechanism of transcription termination from observations of single RNA polymerase molecules. Proc Natl Acad Sci 96: 13124-13129.
149. Yudkovsky N, Ranish JA, Hahn S. 2000. A transcription reinitiation intermediate that is stabilized by activator. Nature 408: 225-229.
150. Yunger S, Rosenfeld L, Garini Y, Shav-Tal Y. 2010. Single-allele analysis of transcription kinetics in living mammalian cells. Nat Methods 7: 631-633.
151. Zenklusen D, Larson DR, Singer RH. 2008. Single-RNA counting reveals alternative modes of gene expression in yeast. Nat Struct Mol Biol 15: 1263-1271.
152. Zhang Z, Revyakin A, Grimm JB, Lavis LD, Tjian R. 2014. Singlemolecule tracking of the transcription cycle by sub-second RNA detection. Elife 3: 1-20.
153. Zhao ZW, Roy R, Gebhardt JCM, Suter DM, Chapman AR, Xie XS. 2014. Spatial organization ofRNApolymerase II inside amammalian cell nucleus revealed by reflected light-sheet superresolution microscopy. Proc Natl Acad Sci 111: 681-686.