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Discontinuous transcription

. 2018 Jan 01 ; 9 (1) : 149-160.

Language English Country United States Media print

Document type Journal Article, Review

Numerous studies based on new single-cell and single-gene techniques show that individual genes can be transcribed in short bursts or pulses accompanied by changes in pulsing frequencies. Since so many examples of such discontinuous or fluctuating transcription have been found from prokaryotes to mammals, it now seems to be a common mode of gene expression. In this review we discuss the occurrence of the transcriptional fluctuations, the techniques used for their detection, their putative causes, kinetic characteristics, and probable physiological significance.

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Coulon A, Chow CC, Singer RH, et al.. Eukaryotic transcriptional dynamics: from single molecules to cell populations. Nat Rev Genet. 2013;14(8):572–584. https://doi.org/10.1038/nrg3484. PubMed DOI PMC

McKnight SL, Miller OL Jr. Post-replicative nonribosomal transcription units in D. melanogaster embryos. Cell. 1979;17(3):551–563. https://doi.org/10.1016/0092-8674(79)90263-0. PubMed DOI

Chong S, Chen C, Ge H, et al.. Mechanism of transcriptional bursting in bacteria. Cell. 2014;158:314–326. https://doi.org/10.1016/j.cell.2014.05.038. PubMed DOI PMC

Golding I, Paulsson J, Zawilski SM, et al.. Real-time kinetics of gene activity in individual bacteria. Cell. 2005;123:1025–1036. https://doi.org/10.1016/j.cell.2005.09.031. PubMed DOI

Harper CV, Featherstone K, Semprini S, et al.. Spatially coordinated dynamic organisation of prolactin gene expression in living pituitary tissue. J Cell Sci. 2010;123:424–430. https://doi.org/10.1242/jcs.060434. PubMed DOI PMC

Suter DM, Molina N, Gatfield D, et al.. Mammalian genes are transcribed with widely different bursting kinetics. Science. 2011a;332(6028):472–474. https://doi.org/10.1126/science.1198817. PubMed DOI

Bahar Halpern K, Tanami S, Landen S, Chapal M, Szlak L, Hutzler A, Nizhberg A, Itzkovitz S. Bursty gene expression in the intact mammalian liver. Mol Cell. 2015;58:147–156. https://doi.org/10.1016/j.molcel.2015.01.027. PubMed DOI PMC

Little SC, Tikhonov M, Gregor T. Precise developmental gene expression arises from globally stochastic transcriptional activity. Cell. 2013;154:789–800. https://doi.org/10.1016/j.cell.2013.07.025. PubMed DOI PMC

Bothma JP, Garcia HG, Esposito E, et al.. Dynamic regulation of eve stripe 2 expression reveals transcriptional bursts in living Drosophila embryos. Proc Natl Acad Sci USA. 2014;111:10598–10603. https://doi.org/10.1073/pnas.1410022111. PubMed DOI PMC

Chang HH, Hemberg M, Barahona M, et al.. Transcriptome-wide noise controls lineage choice in mammalian progenitor cells. Nature. 2008;453:544–547. https://doi.org/10.1038/nature06965. PubMed DOI PMC

Abranches E, Guedes AMV, Moravec M, et al.. Stochastic NANOG fluctuations allow mouse embryonic stem cells to explore pluripotency. Development. 2014;141:2770–2779. https://doi.org/10.1242/dev.108910. PubMed DOI PMC

Ochiai H, Sugawara T, Sakuma T, et al.. Stochastic promoter activation affects Nanog expression variability in mouse embryonic stem cells. Sci Rep. 2014;4:7125. https://doi.org/10.1038/srep07125. PubMed DOI PMC

Lo MY, Rival-Gervier S, Pasceri P, et al.. Rapid transcriptional pulsing dynamics of high expressing retroviral transgenes in embryonic stem cells. PLoS One. 2012;7(5):e37130. https://doi.org/10.1371/journal.pone.0037130. PubMed DOI PMC

Raj A, Peskin CS, Tranchina D, et al.. Stochastic mRNA synthesis in mammalian cells. Stochastic mRNA synthesis in mammalian cells. Plos Biol. 2006;4:1707–1719. https://doi.org/10.1371/journal.pbio.0040309. PubMed DOI PMC

Dar RD, Razooky BS, Singh A, et al.. Transcriptional burst frequency and burst size are equally modulated across the human genome. PNAS. 2012;109(43):17454–17459. https://doi.org/10.1073/pnas.1213530109. PubMed DOI PMC

Golding I, Cox EC. RNA dynamics in live Escherichia coli cells. Proc Natl Acad Sci USA. 2004;101:11310–11315. https://doi.org/10.1073/pnas.0404443101. PubMed DOI PMC

Chubb JR, Trcek T, Shenoy SM, et al.. Transcriptional pulsing of a developmental gene. Curr Biol. 2006;16:1018–1025. https://doi.org/10.1016/j.cub.2006.03.092. PubMed DOI PMC

Younger S, Rosenfeld L, Garini Y, et al.. Single-allele analysis of transcription kinetics in living mammalian cells. Nat Methods. 2010;7:631–633. https://doi.org/10.1038/nmeth.1482. PubMed DOI

Lionnet T, Czaplinski K, Darzacq X, et al.. A transgenic mouse for in vivo detection of endogenous labeled mRNA. Nat Methods. 2011;8:165–170. https://doi.org/10.1038/nmeth.1551. PubMed DOI PMC

Suter DM, Nacho Molina N, Felix Naef F, et al.. Origins and consequences of transcriptional discontinuity. Curr Opin Cell Biol. 2011b;23(6):657–662. https://doi.org/10.1016/j.ceb.2011.09.004. PubMed DOI

Zenklusen D, Larson DR, Singer RH. Single-RNA counting reveals alternative modes of gene expression in yeast. Nat Struct Mol Biol. 2008;15(12):1263–1271. https://doi.org/10.1038/nsmb.1514. PubMed DOI PMC

Muramoto T, Muller I, Thomas G, et al.. Methylation of H3K4 is required for inheritance of active transcriptional states. Curr Biol. 2010;20:397–406. https://doi.org/10.1016/j.cub.2010.01.017. PubMed DOI

Pliss A, Kuzmin AN, Kachynski AV, et al.. Fluctuations and synchrony of RNA synthesis in nucleoli. Integr Biol (Camb). 2015;7(6):681–692. https://doi.org/10.1039/C5IB00008D. PubMed DOI

Turowski TW, Tollervey D. Transcription by RNA polymerase III: insights into mechanism and regulation. Biochem Soc Trans. 2016;44(5):1367–1375. https://doi.org/10.1042/BST20160062. PubMed DOI PMC

Hornacek M, Kovacik L, Mazel T, et al.. Fluctuations of pol I and fibrillarin contents of the nucleoli. Nucleus. 2017;8:1–12. https://doi.org/10.1080/19491034.2017.1306160. PubMed DOI PMC

Haaf T, Hayman DL, Schmid M. Quantitative determination of rDNA transcription units in vertebrate cells. Exp Cell Res. 1991;193(1):78–86. https://doi.org/10.1016/0014-4827(91)90540-B. PubMed DOI

Haaf T, Ward DC. Inhibition of RNA polymerase II transcription causes chromatin decondensation, loss of nucleolar structure, and dispersion of chromosomal domains. Exp Cell Res. 1996;224(1):163–173. https://doi.org/10.1006/excr.1996.0124. PubMed DOI

Cheutin T, O'Donohue MF, Beorchia A, et al.. Three-dimensional organization of active rRNA genes within nucleolus. J Cell Sci. 2002;115(16):3297–3307. PubMed

Denissov S, Lessard F, Mayer C, et al.. A model for the topology of active ribosomal RNA genes. EMBO Rep. 2011;12(3):231–237. https://doi.org/10.1038/embor.2011.8. PubMed DOI PMC

Reid G, Hübner MR, Métivier R, et al.. Cyclic, proteasome-mediated turnover of unliganded and liganded ER alpha on responsive promoters is an integral feature of estrogen signaling. Mol Cell. 2003;11(3):695–707. https://doi.org/10.1016/S1097-2765(03)00090-X. PubMed DOI

Lahav G, Rosenfeld N, Sigal A, et al.. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet. 2004;36(2):147–150. https://doi.org/10.1038/ng1293. PubMed DOI

Rosbash M, Bradley S, Kadener S, et al.. Transcriptional feedback and definition of the circadian pacemaker in Drosophila and animals. Cold Spring Harb Symp Quant Biol. 2007;72:75–83. https://doi.org/10.1101/sqb.2007.72.062. PubMed DOI

Stratmann M, Suter DM, Molina N, et al.. Circadian Dbp transcription relies on highly dynamic BMAL1-CLOCK interaction with E boxes and requires the proteasome. Mol Cell. 2012;48(2):277–287. https://doi.org/10.1016/j.molcel.2012.08.012. PubMed DOI

Fuda NJ, Ardehali MB, Lis JT. Defining mechanisms that regulate RNA polymerase II transcription in vivo. Nature. 2009;461(7261):186–192. https://doi.org/10.1038/nature08449. PubMed DOI PMC

Femino AM, Fay FS, Fogarty K, et al.. Visualization of single RNA transcripts in situ. Science. 1998;280:585–590. https://doi.org/10.1126/science.280.5363.585. PubMed DOI

Mueller F, Senecal A, Tantale K, et al.. FISH-quant: automatic counting of transcripts in 3D FISH images. Nature Methods. 2013;10:277–278. https://doi.org/10.1038/nmeth.2406. PubMed DOI

Bahar Halpern K, Itzkovitz S. Single molecule approaches for quantifying transcription and degradation rates in intact mammalian tissues. Methods. 2016;98:134–142. https://doi.org/10.1016/j.ymeth.2015.11.015. PubMed DOI

Femino AM, Fogarty K, Lifshitz LM, Carrington W, Singer RH. Visualization of single molecules of mRNA in situ. Methods Enzymol. 2003;361:245–304. https://doi.org/10.1016/S0076-6879(03)61015-3. PubMed DOI

Raj A, van den Bogaard P, Rifkin SA, et al.. Imaging individual mRNA molecules using multiple singly labeled probes. Nat Methods. 2008a;5:877–879. https://doi.org/10.1038/nmeth.1253. PubMed DOI PMC

Chubb JR, Liverpool TB. Bursts and pulses: insights from single cell studies into transcriptional mechanisms. Curr Opin Genet Dev. 2010;20(5):478–484. https://doi.org/10.1016/j.gde.2010.06.009. PubMed DOI

Brown CR, Mao C, Falkovskaia E, Jurica MS, Boeger H. Linking stochastic fluctuations in chromatin structure and gene expression. PLoS Biol. 2013;11(8):e10001621. https://doi.org/10.1371/journal.pbio.1001621. PubMed DOI PMC

Bertrand E, Chartrand P, Schaefer M, et al.. Localization of ASH1 mRNA particles in living yeast. Molecular Cell. 1998;2:437–445. https://doi.org/10.1016/S1097-2765(00)80143-4. PubMed DOI

Bensidoun P, Raymond P, Oeffinger M, et al.. Imaging single mRNAs to study dynamics of mRNA export in the yeast Saccharomyces cerevisiae. Methods. 2016;98:104–114. https://doi.org/10.1016/j.ymeth.2016.01.006. PubMed DOI

Singh A, Razooky B, Cox CD, et al.. Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression. Biophys J. 2010;98(8):32–34. https://doi.org/10.1016/j.bpj.2010.03.001. PubMed DOI PMC

Larson DR, Zenklusen D, Wu B, et al.. Real-time observation of transcription initiation and elongation on an endogenous yeast gene. Science. 2011;332(6028):475–478. https://doi.org/10.1126/science.1202142. PubMed DOI PMC

Grünwald D, Singer RH. In vivo imaging of labelled endogenous β-actin mRNA during nucleocytoplasmic transport. Nature. 2010;467(7315):604–607. https://doi.org/10.1038/nature09438. PubMed DOI PMC

Schmidt U, Basyuk E, Robert MC, et al.. Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation. J Cell Biol. 2011;193(5):819–829. https://doi.org/10.1083/jcb.201009012. PubMed DOI PMC

Coulon A, Larson DR. Fluctuation analysis: dissecting transcriptional kinetics with signal theory. Methods Enzymol. 2016;572:159–191. https://doi.org/10.1016/bs.mie.2016.03.017. PubMed DOI PMC

Shav-Tal Y, Darzacq X, Shenoy SM, et al.. Dynamics of single mRNPs in nuclei of living cells. Science. 2004;304(5678):1797–1800. https://doi.org/10.1126/science.1099754. PubMed DOI PMC

Corrigan AM, Tunnacliffe E, Cannon D, et al.. A continuum model of transcriptional bursting. eLife. 2016;5:e13051. https://doi.org/10.7554/eLife.13051. PubMed DOI PMC

Dar RD, Sydney M. Shaffer SM, Singh A, Razooky BS, Simpson ML, Raj A, Weinberger LS. Transcriptional bursting explains the noise–versus–mean relationship in mRNA and protein levels. PLoS One. 2016;11(7):e0158298. https://doi.org/10.1371/journal.pone.0158298. PubMed DOI PMC

Swain PS, Elowitz MB, Siggia ED. Intrinsic and extrinsic contributions to stochasticity in gene expression. Proc Natl Acad Sci USA. 2002;99(20):12795–12800. https://doi.org/10.1073/pnas.162041399. PubMed DOI PMC

Elowitz MB, Levine AJ, Siggia ED, et al.. Stochastic gene expression in a single cell. Science. 2002;297:1183–1186. https://doi.org/10.1126/science.1070919. PubMed DOI

Elgart V, Jia T, Fenley AT, et al.. Connecting protein and mRNA burst distributions for stochastic models of gene expression. Phys Biol. 2011;8:046001. https://doi.org/10.1088/1478-3975/8/4/046001. PubMed DOI

Li G, Levitus M, Bustamante C, et al.. Rapid spontaneous accessibility of nucleosomal DNA. Nat Struct Mol Biol. 2005;12:46–53. https://doi.org/10.1038/nsmb869. PubMed DOI

Schoenfelder S, Clay I, Fraser Peter. The transcriptional interactome: gene expression in 3D. Curr Opin Genet Dev. 2010;20(2):127–133. https://doi.org/10.1016/j.gde.2010.02.002. PubMed DOI

Stavreva DA, Wiench M, John S, et al.. Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat Cell Biol. 2009;11:1093–1102. https://doi.org/10.1038/ncb1922. PubMed DOI PMC

Paulsson J. Models of stochastic gene expression. Phys Life Rev. 2005;2(2):157–175. https://doi.org/10.1016/j.plrev.2005.03.003. DOI

Ozbudak EM, Thattai M, Kurtser I, et al.. Regulation of noise in the expression of a single gene. Nature Genet. 2002;31:69–73. https://doi.org/10.1038/ng869. PubMed DOI

Blake WJ, Kærn M, Cantor CR, et al.. Noise in eukaryotic gene expression. Nature. 2003;422:633–637. https://doi.org/10.1038/nature01546. PubMed DOI

Raser JM, O'Shea EK. Control of stochasticity in eukaryotic gene expression. Science. 2004;304:1811. https://doi.org/10.1126/science.1098641. PubMed DOI PMC

Becskei A, Kaufmann BB, van Oudenaarden A. Contributions of low molecule number and chromosomal positioning to stochastic gene expression. Nat Genet. 2005;37(9):937–944. https://doi.org/10.1038/ng1616. PubMed DOI

Fukaya T, Lim B, Levine M. Enhancer control of transcriptional bursting. Cell. 2016;166:358–368. https://doi.org/10.1016/j.cell.2016.05.025. PubMed DOI PMC

Gillespie DT. A general method for numerically simulating the stochastic time evolution of coupled chemical reactions. J Comput Phys. 1976;22:403–434. https://doi.org/10.1016/0021-9991(76)90041-3. DOI

Shahrezaei V, Ollivier JF, Swain PS. Coloured extrinsic fluctuations and stochastic gene expression. Mol Syst Biol. 2008;4:196. https://doi.org/10.1038/msb.2008.31. PubMed DOI PMC

Sherman MS, Cohen BA. A computational Framework for analyzing stochasticity in gene expression. PLoS Comput Biol. 2014;10(5):e1003596. https://doi.org/10.1371/journal.pcbi.1003596. PubMed DOI PMC

Peccoud J, Ycart B. Markovian modeling of gene-product synthesis. Theor Popul Biol. 1995;48(2):222–234. https://doi.org/10.1006/tpbi.1995.1027. DOI

Taniguchi Y, Choi PJ, Li GW, et al.. Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science. 2010;329:533–538. https://doi.org/10.1126/science.1188308. PubMed DOI PMC

Tu Y. The nonequilibrium mechanism for ultrasensitivity in a biological switch: sensing by Maxwell's demons. PNAS. 2008;105(33):11737–11741. https://doi.org/10.1073/pnas.0804641105. PubMed DOI PMC

Raj A, van Oudenaarden A. Nature, nurture, or chance: stochastic gene expression and its consequences. Cell. 2008b;135(2):216–226. https://doi.org/10.1016/j.cell.2008.09.050. PubMed DOI PMC

Singer ZS, Yong J, Tischler J, et al.. Dynamic heterogeneity and DNA methylation in embryonic stem cells. Molecular Cell. 2014;55:319–331. https://doi.org/10.1016/j.molcel.2014.06.029. PubMed DOI PMC

Sherman MS, Lorenz K, Lanier MH, et al.. Cell-to-cell variability in the propensity to transcribe explains correlated fluctuations in gene expression. Cell Systems. 2015;1:315–325. https://doi.org/10.1016/j.cels.2015.10.011. PubMed DOI PMC

Harper CV, Finkenstädt B, Woodcock DJ, et al.. Dynamic analysis of stochastic transcription cycles. PLoS Biol. 2011;9(4):e1000607. https://doi.org/10.1371/journal.pbio.1000607. PubMed DOI PMC

Hager GL, Elbi C, Johnson TA, et al.. Chromatin dynamics and the evolution of alternate promoter states. Chromosome Res. 2006;14:107–116. https://doi.org/10.1007/s10577-006-1030-0. PubMed DOI

Metivier R, Penot G, Hubner MR, et al.. Estrogen receptor-α directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell. 2003;115:751–763. https://doi.org/10.1016/S0092-8674(03)00934-6. PubMed DOI

Shang YF, Hu X, DiRenzo J, et al.. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell. 2000;103:843–852. https://doi.org/10.1016/S0092-8674(00)00188-4. PubMed DOI

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. 2002;99:7934–7939. https://doi.org/10.1073/pnas.122004799. PubMed DOI PMC

Zoller B, Nicolas D, Molina N, et al.. Structure of silent transcription intervals and noise characteristics of mammalian genes. Mol Syst Biol. 2015;11(7):823. https://doi.org/10.15252/msb.20156257. PubMed DOI PMC

Larson DR, Fritzsch C, Sun L, et al.. Direct observation of frequency modulated transcription in single cells using light activation. eLife. 2013;2:e00750. https://doi.org/10.7554/eLife.00750. PubMed DOI PMC

Senecal A, Munsky B, Proux F, et al.. Transcription factors modulate c-Fos transcriptional bursts. Cell Rep. 2014;8:75–83. https://doi.org/10.1016/j.celrep.2014.05.053. PubMed DOI PMC

Voss TC, Hager GL. Dynamic regulation of transcriptional states by chromatin and transcription factors. Nat Rev Genet. 2013;15:69–81. https://doi.org/10.1038/nrg3623. PubMed DOI PMC

Newman JR, Ghaemmaghami S, Ihmels J, et al.. Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature. 2006;441:840–846. https://doi.org/10.1038/nature04785. PubMed DOI

Hnisz D, Shrinivas K, Young RA, et al.. A phase separation model for transcriptional control. Cell. 2017;169(1):13–23. https://doi.org/10.1016/j.cell.2017.02.007. PubMed DOI PMC

Jonkers I, Kwak H, Lis JT. Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons. eLife. 2014;3:e02407. https://doi.org/10.7554/eLife.02407. PubMed DOI PMC

Core LJ, Lis JT. Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science. 2008;319(5871):1791–1792. https://doi.org/10.1126/science.1150843. PubMed DOI PMC

Rahl PB, Lin CY, Seila AC, et al.. c-Myc regulates transcriptional pause release. Cell. 2010;141(3):432–445. https://doi.org/10.1016/j.cell.2010.03.030. PubMed DOI PMC

Birse CE, Lee BA, Hansen K, et al.. Transcriptional termination signals for RNA polymerase II in fission yeast. EMBO J. 1997;16(12):3633–3643. https://doi.org/10.1093/emboj/16.12.3633. PubMed DOI PMC

Edenberg ER, Downey M, Toczyski D. Polymerase stalling during replication, transcription and translation. Curr Biol. 2014;24(10):445–452. https://doi.org/10.1016/j.cub.2014.03.060. PubMed DOI

Herbert KM, La Porta A, Wong BJ, et al.. Sequence-resolved detection of pausing by single RNA polymerase molecules. Cell. 2006;125(6):1083–1094. https://doi.org/10.1016/j.cell.2006.04.032. PubMed DOI PMC

Shaevitz JW, Abbondanzieri EA, Landick R, et al.. Backtracking by single RNA polymerase molecules observed at near-base-pair resolution. Nature. 2003;426(6967):684–687. https://doi.org/10.1038/nature02191. PubMed DOI PMC

Zenkin N, Yuzenkova Y, Severinov K. Transcript-assisted transcriptional proofreading. Science. 2006;313(5786):518–520. https://doi.org/10.1126/science.1127422. PubMed DOI

Greive SJ, von Hippel PH. Thinking quantitatively about transcriptional regulation. Nat Rev Mol Cell Biol. 2005;6(3):221–232. https://doi.org/10.1038/nrm1588. PubMed DOI

Golding I. Decision making in living cells: lessons from a simple system. Annu Rev Biophys. 2011;40:63–80. https://doi.org/10.1146/annurev-biophys-042910-155227. PubMed DOI PMC

Schibler U, Marcu KB, Perry RP. The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells. Cell. 1978;15(4):1495–1509. https://doi.org/10.1016/0092-8674(78)90072-7. PubMed DOI

Dey SS, Foley JE, Limsirichai P, et al.. Orthogonal control of expression mean and variance by epigenetic features at different genomic loci. Mol Syst Biol. 2015;11(5):806. https://doi.org/10.15252/msb.20145704. PubMed DOI PMC

Cai L, Friedman N, Xie XS. Stochastic protein expression in individual cells at the single molecule level. Nature. 2006;440:358–362. https://doi.org/10.1038/nature04599. PubMed DOI

Selinger DW, Saxena RM, Cheung KJ, et al.. Global RNA half-life analysis in Escherichia coli reveals positional patterns of transcript degradation. Genome Res. 2003;13:216–223. https://doi.org/10.1101/gr.912603. PubMed DOI PMC

Mata J, Marguerat S, Bahler J. Post-transcriptional control of gene expression: a genome-wide perspective. Trends Biochem Sci. 2005;30:506–514. https://doi.org/10.1016/j.tibs.2005.07.005. PubMed DOI

Belle A, Tanay A, Bitincka L, et al.. Quantification of protein half-lives in the budding yeast proteome. Proc Natl Acad Sci USA. 2006;103:13004–13009. https://doi.org/10.1073/pnas.0605420103. PubMed DOI PMC

Eldar A, Elowitz MB. Functional roles for noise in genetic circuits. Nature. 2010;467:167–173. https://doi.org/10.1038/nature09326. PubMed DOI PMC

Maamar H, Raj A, Dubnau D. Noise in gene expression determines cell fate in Bacillus subtilis. Science. 2007;317:526–529. https://doi.org/10.1126/science.1140818. PubMed DOI PMC

Zong C, So LH, Sepulveda LA, et al.. Lysogen stability is determined by the frequency of activity bursts from the fate-determining gene. Mol Syst Biol. 2010;6:440. https://doi.org/10.1038/msb.2010.96. PubMed DOI PMC

Balaban NQ, Merrin J, Chait R, et al.. Bacterial persistence as a phenotypic switch. Science. 2004;305(5690):1622–1625. https://doi.org/10.1126/science.1099390. PubMed DOI

Brock A, Chang H, Huang S. Non-genetic heterogeneity–a mutation-independent driving force for the somatic evolution of tumours. Nat Rev Genet. 2009;10(5):336–342. https://doi.org/10.1038/nrg2556. PubMed DOI

Sharma SV, Lee DY, Li B, et al.. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell. 2010;141(1):69–80. https://doi.org/10.1016/j.cell.2010.02.027. PubMed DOI PMC

Chalancon G, Ravarani CN, Balaji S, et al.. Interplay between gene expression noise and regulatory network architecture. Trends Genet. 2012;28(5):221–232. https://doi.org/10.1016/j.tig.2012.01.006. PubMed DOI PMC

Sigal A, Milo R, Cohen A, et al.. Variability and memory of protein levels in human cells. Nature. 2006;444:643–646. https://doi.org/10.1038/nature05316. PubMed DOI

Chubb JR. Gene regulation: stable noise. Curr Biol. 2016;26(2):R61–R64. https://doi.org/10.1016/j.cub.2015.12.002. PubMed DOI

Wernet MF, Mazzoni EO, Celik A, et al.. Stochastic spineless expression creates the retinal mosaic for colour vision. Nature. 2006;440:174–180. https://doi.org/10.1038/nature04615. PubMed DOI PMC

Lesch BJ, Gehrke AR, Bulyk ML, et al.. Transcriptional regulation and stabilization of left-right neuronal identity in C. elegans. Genes Dev. 2009;23:345–358. https://doi.org/10.1101/gad.1763509. PubMed DOI PMC

Wang L, Walker BL, Iannaccone S, et al.. Bistable switches control memory and plasticity in cellular differentiation. Proc Natl Acad Sci USA. 2009;106:6638–6643. https://doi.org/10.1073/pnas.0806137106. PubMed DOI PMC

Paulsson J, Nordström K, Ehrenberg M. Requirements for rapid plasmid ColE1 copy number adjustments: a mathematical model of inhibition modes and RNA turnover rates. Plasmid. 1998;39(3):215–234. https://doi.org/10.1006/plas.1998.1338. PubMed DOI

Paulsson J, Ehrenberg M. Random signal fluctuations can reduce random fluctuations in regulated components of chemical regulatory networks. Phys Rev Lett. 2000;84(23):5447–5450. https://doi.org/10.1103/PhysRevLett.84.5447. PubMed DOI

El-Samad H, Khammash M. Regulated degradation is a mechanism for suppressing stochastic fluctuations in gene regulatory networks. Biophys J. 2006;90(10):3749–3761. https://doi.org/10.1529/biophysj.105.060491. PubMed DOI PMC

Coulon A, Ferguson ML, de Turris V, et al.. Kinetic competition during the transcription cycle results in stochastic RNA processing. Elife. 2014;3:e03939. https://doi.org/10.7554/eLife.03939. PubMed DOI PMC

Mayer A, Landry HM, Churchman LS. Pause & go: from the discovery of RNA polymerase pausing to its functional implications. Curr Opin Cell Biol. 2017;46:72–80. https://doi.org/10.1016/j.ceb.2017.03.002. PubMed DOI PMC

Nicolas D, Phillips NE, Naef F. What shapes eukaryotic transcriptional bursting? Mol BioSyst. 2017;13:1280. https://doi.org/10.1039/C7MB00154A. PubMed DOI

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