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Eukaryotic transcriptional dynamics: from single molecules to cell populations

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Coulon, Antoine, Chow, Carson C., Singer, Robert H., Larson, Daniel R.·2013·Nature Reviews Genetics
DOI 10.1038/nrg3484PMC PMC3807637
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Abstract

Transcriptional regulation is achieved through combinatorial interactions between regulatory elements in the human genome and a vast range of factors that modulate the recruitment and activity of RNA polymerase. Experimental approaches for studying transcription in vivo now extend from single-molecule techniques to genome-wide measurements. Parallel to these developments is the need for testable quantitative and predictive models for understanding gene regulation. These conceptual models must also provide insight into the dynamics of transcription and the variability that is observed at the single-cell level. In this Review, we discuss recent results on transcriptional regulation and also the models those results engender. We show how a non-equilibrium description informs our view of transcription by explicitly considering time- and energy-dependence at the molecular level.

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  • Transcription occurs in intermittent bursts that give rise to variable mRNA numbers in single cells.

    “Transcription occurs in intermittent bursts35 that give rise to variable mRNA numbers in single cells.”

    From Nonlinear control of transcription through enhancer–promoter interactions (2022) · cites this paper as [35]

  • Enhancer strength modulates the ability of the promoter to turn on.

    “This further strengthens our interpretation that enhancer strength modulates the ability of the promoter to turn on, possibly by regulating chromatin state, transcription factor binding or RNA polymerase II dynamics at the promoter35,44 .”

    From Nonlinear control of transcription through enhancer–promoter interactions (2022) · cites this paper as [35]

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  1. [2]Dundr M A kinetic framework for a mammalian RNA polymerase in vivo Science 298 1623 1626 2002 12446911
  2. [3]Dion MF Dynamics of replication-independent histone turnover in budding yeast Science 315 1405 1408 2007 This study measured the turnover rates of core histones on a genome-wide scale and reported dwell times on the order of tens of minutes that varied substantially between genomic locations 17347438
  3. [4]Métivier R Penot G Hübner MR Reid G Brand H Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter Cell 115 751 763 2003 14675539
  4. [5]Chubb JR Trcek T Shenoy SM Singer RH Transcriptional pulsing of a developmental gene Curr Biol 16 1018 1025 2006 16713960 PMC4764056
  5. [6]Larson DR What do expression dynamics tell us about the mechanism of transcription? Curr Op Genet Dev 21 591 599 2011 21862317 PMC3475196
  6. [7]Stamatoyannopoulos JA What does our genome encode? Genome Res 22 1602 1611 2012 22955972 PMC3431477
  7. [8]Johnson DS Mortazavi A Myers RM Wold B Genome-wide mapping of in vivo protein-DNA interactions Science 316 1497 1502 2007 The first article to report genome-wide binding of a chromatin-interacting factor by ChIP followed by high-throughput sequencing (ChIP–seq) 17540862
  8. [9]Rhee HS Pugh BF Comprehensive genome-wide protein-DNA interactions detected at single-nucleotide resolution Cell 147 1408 1419 2011 22153082 PMC3243364
  9. [11]van Royen ME Zotter A Ibrahim SM Geverts B Houtsmuller AB Nuclear proteins: finding and binding target sites in chromatin Chromosome Res 19 83 98 2011 21181254
  10. [12]Raj A van Oudenaarden A Nature, nurture, or chance: stochastic gene expression and its consequences Cell 135 216 226 2008 18957198 PMC3118044
  11. [13]Soutoglou E Talianidis I Coordination of PIC assembly and chromatin remodeling during differentiation-induced gene activation Science 295 1901 1904 2002 11884757
  12. [14]Shang YF Hu X DiRenzo J Lazar MA Brown M Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription Cell 103 843 852 2000 11136970
  13. [15]Sharma D Fondell JD Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo Proc Natl Acad Sci USA 99 7934 7939 2002 12034878 PMC122998
  14. [16]Métivier R Cyclical DNA methylation of a transcriptionally active promoter Nature 452 45 50 2008 18322525
  15. [17]Elf J Li GW Xie XS Probing transcription factor dynamics at the single-molecule level in a living cell Science 316 1191 1194 2007 17525339 PMC2853898
  16. [18]Larson DR Zenklusen D Wu B Chao JA Singer RH Real-time observation of transcription initiation and elongation on an endogenous yeast gene Science 332 475 478 2011 The first direct observation of RNA synthesis in living cells at the single-transcript level, which revealed the kinetics of initiation and elongation 21512033 PMC3152976
  17. [20]Cairns BR The logic of chromatin architecture and remodelling at promoters Nature 461 193 198 2009 19741699
  18. [21]Weake VM Workman JL Inducible gene expression: diverse regulatory mechanisms Nature Rev Genet 11 426 437 2010 20421872
  19. [22]Buratowski S Hahn S Guarente L Sharp PA Five intermediate complexes in transcription initiation by RNA polymerase II Cell 56 549 561 1989 2917366
  20. [23]Roeder RG Transcriptional regulation and the role of diverse coactivators in animal cells FEBS Lett 579 909 915 2005 15680973
  21. [24]Thomas MC Chiang CM The general transcription machinery and general cofactors Crit Rev Biochem Mol Biol 41 105 178 2006 16858867
  22. [25]Dieci G Sentenac A Detours and shortcuts to transcription reinitiation Trends Biochem Sci 28 202 209 2003 12713904
  23. [26]Esnault C Mediator-dependent recruitment of TFIIH modules in preinitiation complex Mol Cell 31 337 346 2008 18691966
  24. [27]Sikorski TW Buratowski S The basal initiation machinery: beyond the general transcription factors Curr Opin Cell Biol 21 344 351 2009 19411170 PMC2692371
  25. [28]Kim S Shevde NK Pike JW 1,25-Dihydroxyvitamin D3 stimulates cyclic vitamin D receptor/retinoid X receptor DNA-binding, co-activator recruitment, and histone acetylation in intact osteoblasts J Bone Miner Res 20 305 317 2004 15647825
  26. [29]Nagaich AK Walker DA Wolford R Hager GL Rapid periodic binding and displacement of the glucocorticoid receptor during chromatin remodeling Mol Cell 14 163 174 2004 This study presented a minimalist in vitro system that recapitulated the recruitment of a remodeller to a chromatin template by GR, thus resulting in its own eviction following remodelling. This system displays an intrinsic periodic behaviour 15099516
  27. [30]Qiu Y HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription Mol Cell 22 669 679 2006 16762839
  28. [31]John S Kinetic complexity of the global response to glucocorticoid receptor action Endocrinology 150 1766 1774 2009 19131569 PMC2659280
  29. [32]Li G Highly compacted chromatin formed in vitro reflects the dynamics of transcription activation in vivo Mol Cell 38 41 53 2010 20385088 PMC3641559
  30. [33]Carroll JS Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1 Cell 122 33 43 2005 16009131
  31. [34]Laganière J Location analysis of estrogen receptor a target promoters reveals that FOXA1 defines a domain of the estrogen response Proc Natl Acad Sci USA 102 11651 11656 2005 16087863 PMC1183449
  32. [35]Lupien M FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription Cell 132 958 970 2008 18358809 PMC2323438
  33. [36]Welboren WJ ChIP-Seq of ERα and RNA polymerase II defines genes differentially responding to ligands EMBO J 28 1418 1428 2009 19339991 PMC2688537
  34. [37]Hurtado A Holmes KA Ross-Innes CS Schmidt D Carroll JS FOXA1 is a key determinant of estrogen receptor function and endocrine response Nature Genet 43 27 33 2010 21151129 PMC3024537
  35. [38]Kong SL Li G Loh SL Sung WK Liu ET Cellular reprogramming by the conjoint action of ERα, FOXA1, and GATA3 to a ligand-inducible growth state Mol Syst Biol 7 526 2011 21878914 PMC3202798
  36. [39]Cirillo LA Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome EMBO J 17 244 254 1998 9427758 PMC1170375
  37. [40]Cirillo LA Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4 Mol Cell 9 279 289 2002 11864602
  38. [41]Perlmann T Eriksson P Wrange O Quantitative analysis of the glucocorticoid receptor-DNA interaction at the mouse mammary tumor virus glucocorticoid response element J Biol Chem 265 17222 17229 1990 2170368
  39. [42]Zabel U Baeuerle PA Purified human IκB can rapidly dissociate the complex of the NF-κB transcription factor with its cognate DNA Cell 61 255 265 1990 2184941
  40. [43]Lieberman BA Nordeen SK DNA intersegment transfer, how steroid receptors search for a target site J Biol Chem 272 1061 1068 1997 8995403
  41. [44]Yie JM Merika M Munshi N Chen GY Thanos D The role of HMG I(Y) in the assembly and function of the IFN-β enhanceosome EMBO J 18 3074 3089 1999 10357819 PMC1171389
  42. [45]Stenoien DL FRAP reveals that mobility of oestrogen receptor-α is ligand-and proteasome-dependent Nature Cell Biol 3 15 23 2001 11146621
  43. [47]Normanno D Dahan M Darzacq X Intra-nuclear mobility and target search mechanisms of transcription factors: a single-molecule perspective on gene expression Biochim Biophys Acta Gene Regulatory Mechs 1819 482 493 2012 22342464
  44. [48]Darzacq X Imaging transcription in living cells Annu Rev Biophys 38 173 196 2009 19416065 PMC3166783
  45. [49]Sung MH McNally JG Live cell imaging and systems biology Wiley Interdiscip Rev Syst Biol Med 3 167 182 2010 20730797 PMC2992103
  46. [50]Hager GL McNally JG Misteli T Transcription dynamics Mol Cell 35 741 753 2009 19782025 PMC6326382
  47. [51]Mueller F Mazza D Stasevich TJ McNally JG FRAP and kinetic modeling in the analysis of nuclear protein dynamics: what do we really know? Curr Opin Cell Biol 22 403 411 2010 20413286 PMC2916960
  48. [52]Stasevich TJ Cross-validating FRAP and FCS to quantify the impact of photobleaching on in vivo binding estimates Biophys J 99 3093 3101 2010 21044608 PMC2966010
  49. [53]Nalley K Johnston SA Kodadek T Proteolytic turnover of the Gal4 transcription factor is not required for function in vivo Nature 442 1054 1057 2006 16929306
  50. [54]Deal RB Henikoff JG Henikoff S Genome-wide kinetics of nucleosome turnover determined by metabolic labeling of histones Science 328 1161 1164 2010 20508129 PMC2879085
  51. [55]Rayasam GV Ligand-specific dynamics of the progesterone receptor in living cells and during chromatin remodeling in vitro Mol Cell Biol 25 2406 2418 2005 15743833 PMC1061598
  52. [56]Agresti A Scaffidi P Riva A Caiolfa VR Bianchi ME GR and HMGB1 interact only within chromatin and influence each other's residence time Mol Cell 18 109 121 2005 15808513
  53. [57]Yao J Munson KM Webb WW Lis JT Dynamics of heat shock factor association with native gene loci in living cells Nature 442 1050 1053 2006 16929308
  54. [58]Darzacq X In vivo dynamics of RNA polymerase II transcription Nature Struct Mol Biol 14 796 806 2007 17676063 PMC4942130
  55. [59]Gorski SA Snyder SK John S Grummt I Misteli T Modulation of RNA polymerase assembly dynamics in transcriptional regulation Mol Cell 30 486 497 2008 18498750 PMC2441649
  56. [60]Sprouse RO Regulation of TATA-binding protein dynamics in living yeast cells Proc Natl Acad Sci USA 105 13304 13308 2008 18765812 PMC2533185
  57. [61]Erdel F Schubert T Marth C Längst G Rippe K Human ISWI chromatin-remodeling complexes sample nucleosomes via transient binding reactions and become immobilized at active sites Proc Natl Acad Sci USA 107 19873 19878 2010 20974961 PMC2993390
  58. [62]Harper CV Dynamic analysis of stochastic transcription cycles PLoS Biol 9 e1000607 2011 This paper presents inference of single-gene activity from fluctuations of protein expression levels. Two identical genes monitored simultaneously in the same cell display uncorrelated periodic activity, thus indicating a cis-originating mechanism that is consistent with a molecular ratchet 21532732 PMC3075210
  59. [63]Suter DM Mammalian genes are transcribed with widely different bursting kinetics Science 332 472 474 2011 This study presents inference of single-gene activity from fluctuations of protein expression levels. Distributions of active and inactive times in gene bursting indicate refractoriness in gene reactivation, thus reflecting a multistep sequential process 21415320
  60. [64]Levsky JM Singer RH Gene expression and the myth of the average cell Trends Cell Biol 13 4 6 2003 12480334
  61. [66]Karpova TS Concurrent fast and slow cycling of a transcriptional activator at an endogenous promoter Science 319 466 469 2008 18218898
  62. [67]Voss TC Combinatorial probabilistic chromatin interactions produce transcriptional heterogeneity J Cell Sci 122 345 356 2009 19126674 PMC2724732
  63. [68]Viñuelas J Quantifying the contribution of chromatin dynamics to stochastic gene expression reveals long, locus-dependent periods between transcriptional bursts BMC Biol 11 15 2013 23442824 PMC3635915
  64. [69]von Hippel PH From “simple” DNA-protein interactions to the macromolecular machines of gene expression Annu Rev Biophys Biomol Struct 36 79 105 2007 17477836 PMC2660389
  65. [70]Field Y Distinct modes of regulation by chromatin encoded through nucleosome positioning signals PLoS Comput Biol 4 e1000216 2008 18989395 PMC2570626
  66. [71]Raveh-Sadka T Levo M Segal E Incorporating nucleosomes into thermodynamic models of transcription regulation Genome Res 19 1480 1496 2009 19451592 PMC2720181
  67. [72]Segal E Widom J From DNA sequence to transcriptional behaviour: a quantitative approach Nature Rev Genet 10 443 456 2009 19506578 PMC2719885
  68. [73]Lam FH Steger DJ O'Shea EK Chromatin decouples promoter threshold from dynamic range Nature 453 246 250 2008 18418379 PMC2435410
  69. [74]Kingston RE Narlikar GJ ATP-dependent remodeling and acetylation as regulators of chromatin fluidity Genes Dev 13 2339 2352 1999 10500090
  70. [75]Partensky PD Narlikar GJ Chromatin remodelers act globally, sequence positions nucleosomes locally J Mol Biol 391 12 25 2009 19450608 PMC2813840
  71. [77]Clapier CR Cairns BR The biology of chromatin remodeling complexes Annu Rev Biochem 78 273 304 2009 19355820
  72. [78]Lemaire V Lee C Lei J Métivier R Glass L Sequential recruitment and combinatorial assembling of multiprotein complexes in transcriptional activation Phys Rev Lett 96 198102 2006 16803143
  73. [79]Coulon A Gandrillon O Beslon G On the spontaneous stochastic dynamics of a single gene: complexity of the molecular interplay at the promoter BMC Systems Biol 4 2 2010 PMC2832887 20064204
  74. [80]Kim HD O'Shea EK A quantitative model of transcription factor-activated gene expression Nature Struct Mol Biol 15 1192 1198 2008 18849996 PMC2696132
  75. [81]Boettiger AN Ralph PL Evans SN Transcriptional regulation: effects of promoter proximal pausing on speed, synchrony and reliability PLoS Comput Biol 7 e1001136 2011 21589887 PMC3093350
  76. [82]Schwabe A Rybakova KN Bruggeman FJ Transcription stochasticity of complex gene regulation models Biophys J 103 1152 1161 2012 22995487 PMC3446772
  77. [83]Dobrzynski M Bruggeman FJ Elongation dynamics shape bursty transcription and translation Proc Natl Acad Sci USA 106 2583 2588 2009 19196995 PMC2650307
  78. [84]Sanchez A Kondev J Transcriptional control of noise in gene expression Proc Natl Acad Sci USA 105 5081 5086 2008 18353986 PMC2278180
  79. [85]Boeger H Griesenbeck J Kornberg RD Nucleosome retention and the stochastic nature of promoter chromatin remodeling for transcription Cell 133 716 726 2008 18485878 PMC2409070
  80. [86]Müller D Stelling J Precise regulation of gene expression dynamics favors complex promoter architectures PLoS Comput Biol 5 e1000279 2009 19180182 PMC2615112
  81. [87]Kaplan N The DNA-encoded nucleosome organization of a eukaryotic genome Nature 458 362 366 2009 19092803 PMC2658732
  82. [88]Valouev A Determinants of nucleosome organization in primary human cells Nature 474 516 520 2011 21602827 PMC3212987
  83. [89]Yuan GC Genome-scale identification of nucleosome positions in S cerevisiae Science 309 626 630 2005 15961632
  84. [90]Jiang C Pugh BF Nucleosome positioning and gene regulation: advances through genomics Nature Rev Genet 10 161 172 2009 19204718 PMC4860946
  85. [91]Segal E A genomic code for nucleosome positioning Nature 442 772 778 2006 16862119 PMC2623244
  86. [92]Kornberg RD Stryer L Statistical distributions of nucleosomes: nonrandom locations by a stochastic mechanism Nucleic Acids Res 16 6677 6690 1988 3399412 PMC338322
  87. [93]Vaillant C Audit B Arneodo A Experiments confirm the influence of genome long-range correlations on nucleosome positioning Phys Rev Lett 99 218103 2007 18233262
  88. [94]Chevereau G Palmeira L Thermes C Arneodo A Vaillant C Thermodynamics of intragenic nucleosome ordering Phys Rev Lett 103 188103 2009 19905836
  89. [95]Weiner A Hughes A Yassour M Rando OJ Friedman N High-resolution nucleosome mapping reveals transcription-dependent promoter packaging Genome Res 20 90 100 2010 19846608 PMC2798834
  90. [96]Zhang Z A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome Science 332 977 980 2011 This study reports an in vitro reconstitution of nucleosome positioning patterns over gene bodies that mimic in vivo positions. The need for ATP to obtain this result demonstrates the non-equilibrium nature of nucleosome positioning 21596991 PMC4852979
  91. [97]Sprague BL Analysis of binding at a single spatially localized cluster of binding sites by fluorescence recovery after photobleaching Biophys J 91 1169 1191 2006 16679358 PMC1518639
  92. [99]Elbi C Molecular chaperones function as steroid receptor nuclear mobility factors Proc Natl Acad Sci USA 101 2876 2881 2004 14978266 PMC365713
  93. [100]Stavreva DA Muller WG Hager GL Smith CL McNally JG Rapid glucocorticoid receptor exchange at a promoter is coupled to transcription and regulated by chaperones and proteasomes Mol Cell Biol 24 2682 2697 2004 15024059 PMC371101
  94. [101]Bosisio D A hyper-dynamic equilibrium between promoter-bound and nucleoplasmic dimers controls NF-κB-dependent gene activity EMBO J 25 798 810 2006 16467852 PMC1383558
  95. [102]Karpova TS Chen TY Sprague BL McNally JG Dynamic interactions of a transcription factor with DNA are accelerated by a chromatin remodeller EMBO Rep 5 1064 1070 2004 15514679 PMC1299176
  96. [103]Johnson TA Elbi C Parekh BS Hager GL John S Chromatin remodeling complexes interact dynamically with a glucocorticoid receptor-regulated promoter Mol Biol Cell 19 3308 3322 2008 18508913 PMC2488306
  97. [104]Fletcher TM ATP-dependent mobilization of the glucocorticoid receptor during chromatin remodeling Mol Cell Biol 22 3255 3263 2002 11971959 PMC133787
  98. [106]Ko MS Nakauchi H Takahashi N The dose dependence of glucocorticoid-inducible gene expression results from changes in the number of transcriptionally active templates EMBO J 9 2835 2842 1990 2167833 PMC551995
  99. [107]Walters MC Enhancers increase the probability but not the level of gene expression Proc Natl Acad Sci USA 92 7125 7129 1995 7624382 PMC41484
  100. [108]White MR Real-time analysis of the transcriptional regulation of HIV and hCMV promoters in single mammalian cells J Cell Sci 108 441 455 1995 7768992
  101. [109]Paszek P Population robustness arising from cellular heterogeneity Proc Natl Acad Sci USA 107 11644 11649 2010 20534546 PMC2895068
  102. [110]Raj A Rifkin SA Andersen E van Oudenaarden A Variability in gene expression underlies incomplete penetrance Nature 463 913 918 2010 20164922 PMC2836165
  103. [111]Swain PS Elowitz MB Siggia ED Intrinsic and extrinsic contributions to stochasticity in gene expression Proc Natl Acad Sci USA 99 12795 12800 2002 12237400 PMC130539
  104. [113]Paulsson J Summing up the noise in gene networks Nature 427 415 418 2004 14749823
  105. [115]Becskei A Kaufmann BB van Oudenaarden A Contributions of low molecule number and chromosomal positioning to stochastic gene expression Nature Genet 37 937 944 2005 16086016
  106. [116]Sigal A Variability and memory of protein levels in human cells Nature 444 643 646 2006 17122776
  107. [117]Skupsky R Burnett JC Foley JE Schaffer DV Arkin AP HIV promoter integration site primarily modulates transcriptional burst size rather than frequency PLoS Comput Biol 6 e1000952 2010 20941390 PMC2947985
  108. [118]Stevense M Muramoto T Muller I Chubb JR Digital nature of the immediate-early transcriptional response Development 137 579 584 2010 20110323 PMC2827614
  109. [119]Muramoto T Müller I Thomas G Melvin A Chubb JR Methylation of H3K4 Is required for inheritance of active transcriptional states Curr Biol 20 397 406 2010 20188556
  110. [121]Lionnet T Wu B Grünwald D Singer RH Larson DR Nuclear physics: quantitative single-cell approaches to nuclear organization and gene expression Cold Spring Harb Symp Quant Biol 75 113 126 2010 21502409 PMC3145213
  111. [123]Golding I Decision making in living cells: lessons from a simple system Annu Rev Biophys 40 63 80 2011 21545284 PMC4465489
  112. [124]Newman JRS Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise Nature 441 840 846 2006 16699522
  113. [125]Gandhi SJ Zenklusen D Lionnet T Singer RH Transcription of functionally related constitutive genes is not coordinated Nature Struct Mol Biol 18 27 34 2010 21131977 PMC3058351
  114. [126]So LH General properties of transcriptional time series in Escherichia coli Nature Genet 43 554 560 2011 PMC3102781 21532574
  115. [127]Dunlop MJ Cox RS Levine JH Murray RM Elowitz MB Regulatory activity revealed by dynamic correlations in gene expression noise Nature Genet 40 1493 1498 2008 19029898 PMC2829635
  116. [128]Bertrand E Localization of ASH1 mRNA particles in living yeast Mol Cell 2 437 445 1998 The first observation of RNA particles in living cells using the MS2 RNA-labelling technique 9809065
  117. [129]Larson DR Singer RH Zenklusen D A single molecule view of gene expression Trends Cell Biol 19 630 637 2009 19819144 PMC2783999
  118. [130]Grünwald D Singer RH In vivo imaging of labelled endogenous β-actin mRNA during nucleocytoplasmic transport Nature 467 604 607 2010 20844488 PMC3005609
  119. [132]Lionnet T A transgenic mouse for in vivo detection of endogenous labeled mRNA Nature Methods 8 165 170 2011 21240280 PMC3076588
  120. [133]Schmidt U Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation J Cell Biol 193 819 829 2011 21624952 PMC3105549
  121. [135]Blake WJ Kærn M Cantor CR Collins JJ Noise in eukaryotic gene expression Nature 422 633 637 2003 12687005
  122. [136]Batenchuk C Chromosomal position effects are linked to Sir2-mediated variation in transcriptional burst size Biophys J 100 L56 L58 2011 21575565 PMC3093560
  123. [137]Singh A Razooky B Cox CD Simpson ML Weinberger LS Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression Biophys J 98 L32 L34 2010 20409455 PMC2856162
  124. [138]Pedraza JM Paulsson J Effects of molecular memory and bursting on fluctuations in gene expression Science 319 339 343 2008 18202292
  125. [139]Métivier R Reid G Gannon F Transcription in four dimensions: nuclear receptor-directed initiation of gene expression EMBO Rep 7 161 167 2006 16452926 PMC1369254
  126. [140]Moffitt JR Intersubunit coordination in a homomeric ring ATPase Nature 457 446 451 2009 19129763 PMC2716090
  127. [142]Weber A Liu JH Collins I Levens D TFIIH operates through an expanded proximal promoter to fine-tune c-myc expression Mol Cell Biol 25 147 161 2005 15601838 PMC538784
  128. [143]Kimura H Sugaya K Cook PR The transcription cycle of RNA polymerase II in living cells J Cell Biol 159 777 782 2002 12473686 PMC2173384
  129. [144]Singh J Padgett RA Rates of in situ transcription and splicing in large human genes Nature Struct Mol Biol 16 1128 1133 2009 19820712 PMC2783620
  130. [145]Hager GL Chromatin dynamics and the evolution of alternate promoter states Chromosome Res 14 107 116 2006 16506100
  131. [146]Reid G Gallais R Métivier R Marking time: the dynamic role of chromatin and covalent modification in transcription Int J Biochem Cell Biol 41 155 163 2009 18805503
  132. [148]Ong KM Blackford JA Kagan BL Simons SS Chow CC A theoretical framework for gene induction and experimental comparisons Proc Natl Acad Sci USA 107 7107 7112 2010 20351279 PMC2872427
  133. [149]Kininis M Genomic analyses of transcription factor binding, histone acetylation, and gene expression reveal mechanistically distinct classes of estrogen-regulated promoters Mol Cell Biol 27 5090 5104 2007 17515612 PMC1951957
  134. [150]Kang Z Pirskanen A Jänne OA Palvimo JJ Involvement of proteasome in the dynamic assembly of the androgen receptor transcription complex J Biol Chem 277 48366 48371 2002 12376534
  135. [151]Paszek P Jackson DA White MR Oscillatory control of signalling molecules Curr Opin Genet Dev 20 670 676 2010 20850963
  136. [152]Ferrell JE Tsai TYC Yang Q Modeling the cell cycle: why do certain circuits oscillate? Cell 144 874 885 2011 21414480
  137. [153]Thurman RE The accessible chromatin landscape of the human genome Nature 488 75 82 2012 22955617 PMC3721348
  138. [155]Simons SS Chow CC The road less traveled: New views of steroid receptor action from the path of dose-response curves Mol Cell Endocrinol 348 373 382 2011 21664235 PMC3184374

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Authors
Coulon, A., Chow, C. C., Singer, R. H., & Larson, D. R.
Affiliations
  • National Institutes of Health (US)
  • Albert Einstein College of Medicine (US)
Corresponding author
Larson, Daniel R.
ORCID
Venue
Nature Reviews Genetics
Publisher
Springer Science and Business Media LLC
Published
2013-07-09
Volume
14
Issue
8
Pages
572-584
ISSN
  • 1471-0056 (ISSN-L)
  • 1471-0064
DOI
10.1038/nrg3484
PMC
PMC3807637
OpenAlex
W2066415979
Cited by
309
References
12
Citations by year
2026: 8 · 2025: 23 · 2024: 15 · 2023: 15 · 2022: 14 · 2021: 23 · 2020: 22 · 2019: 29 · 2018: 27 · 2017: 31 · 2016: 31 · 2015: 40 · 2014: 22 · 2013: 9
FWCI
3.20
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Reviews Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • U.S. Public Health Service (84364, 86217)
  • National Institute of General Medical Sciences (R01GM057071, GM57071, R01GM084364, R01GM086217)
  • National Institute of Diabetes and Digestive and Kidney Diseases (ZIADK075069)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
transcriptional regulation, eukaryotic transcription, genome-wide transcription, gene expression regulation, RNA polymerase recruitment, nonequilibrium dynamics, cellular heterogeneity
MeSH terms
Gene Expression Regulation, Humans, DNA-Directed RNA Polymerases, Transcription Factors, Transcription, Genetic, Genome, Human

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