{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:10:30Z","timestamp":1767175830509,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009811","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000}}],"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["R35GM122465"],"award-info":[{"award-number":["R35GM122465"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"national science foundation graduate research fellowship program","award":["DGE-1644868"],"award-info":[{"award-number":["DGE-1644868"]}]},{"name":"norwegian financial mechanism grieg-1 grant","award":["2019\/34\/H\/NZ6\/00699"],"award-info":[{"award-number":["2019\/34\/H\/NZ6\/00699"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"\n Nucleosomes are recognized as key regulators of transcription. However, the relationship between slow nucleosome unwrapping dynamics and bulk transcriptional properties has not been thoroughly explored. Here, an agent-based model that we call the dynamic defect Totally Asymmetric Simple Exclusion Process (ddTASEP) was constructed to investigate the effects of nucleosome-induced pausing on transcriptional dynamics. Pausing due to slow nucleosome dynamics induced RNAPII convoy formation, which would cooperatively prevent nucleosome rebinding leading to bursts of transcription. The mean first passage time (MFPT) and the variance of first passage time (VFPT) were analytically expressed in terms of the nucleosome rate constants, allowing for the direct quantification of the effects of nucleosome-induced pausing on pioneering polymerase dynamics. The mean first passage elongation rate\n \u03b3<\/jats:italic>\n (\n h<\/jats:italic>\n \n c<\/jats:italic>\n <\/jats:sub>\n ,\n h<\/jats:italic>\n \n o<\/jats:italic>\n <\/jats:sub>\n ) is inversely proportional to the MFPT and can be considered to be a new axis of the ddTASEP phase diagram, orthogonal to the classical\n \u03b1\u03b2<\/jats:italic>\n -plane (where\n \u03b1<\/jats:italic>\n and\n \u03b2<\/jats:italic>\n are the initiation and termination rates). Subsequently, we showed that, for\n \u03b2<\/jats:italic>\n = 1, there is a novel jamming transition in the\n \u03b1\u03b3<\/jats:italic>\n -plane that separates the ddTASEP dynamics into initiation-limited and nucleosome pausing-limited regions. We propose analytical estimates for the RNAPII density\n \u03c1<\/jats:italic>\n , average elongation rate\n v<\/jats:italic>\n , and transcription flux\n J<\/jats:italic>\n and verified them numerically. We demonstrate that the intra-burst RNAPII waiting times\n t<\/jats:italic>\n \n in<\/jats:italic>\n <\/jats:sub>\n follow the time-headway distribution of a max flux TASEP and that the average inter-burst interval\n \n \n \n \n \n \n \n \n t<\/mml:mi>\n <\/mml:mrow>\n \n I<\/mml:mi>\n B<\/mml:mi>\n I<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n \u00af<\/mml:mo>\n <\/mml:mover>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n correlates with the index of dispersion\n D<\/jats:italic>\n \n e<\/jats:italic>\n <\/jats:sub>\n . In the limit\n \u03b3<\/jats:italic>\n \u21920, the average burst size reaches a maximum set by the closing rate\n h<\/jats:italic>\n \n c<\/jats:italic>\n <\/jats:sub>\n . When\n \u03b1<\/jats:italic>\n \u226a1, the burst sizes are geometrically distributed, allowing large bursts even while the average burst size\n \n \n \n \n \n \n \n \n N<\/mml:mi>\n <\/mml:mrow>\n \n B<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n \u00af<\/mml:mo>\n <\/mml:mover>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n is small. Last, preliminary results on the relative effects of static and dynamic defects are presented to show that dynamic defects can induce equal or greater pausing than static bottle necks.\n <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009811","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T13:50:27Z","timestamp":1644501027000},"page":"e1009811","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Slow nucleosome dynamics set the transcriptional speed limit and induce RNA polymerase II traffic jams and bursts"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7637-9991","authenticated-orcid":true,"given":"Robert C.","family":"Mines","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3488-2561","authenticated-orcid":true,"given":"Tomasz","family":"Lipniacki","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4978-3531","authenticated-orcid":true,"given":"Xiling","family":"Shen","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"issue":"5584","key":"pcbi.1009811.ref001","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1126\/science.1070919","article-title":"Stochastic gene expression in a single cell","volume":"297","author":"MB Elowitz","year":"2002","journal-title":"Science"},{"issue":"20","key":"pcbi.1009811.ref002","doi-asserted-by":"crossref","first-page":"12795","DOI":"10.1073\/pnas.162041399","article-title":"Intrinsic and extrinsic contributions to stochasticity in gene expression","volume":"99","author":"PS Swain","year":"2002","journal-title":"Proc Natl Acad Sci"},{"issue":"6274","key":"pcbi.1009811.ref003","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1126\/science.aab2956","article-title":"Dynamics of epigenetic regulation at the single-cell level","volume":"351","author":"L Bintu","year":"2016","journal-title":"Science"},{"issue":"2","key":"pcbi.1009811.ref004","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cell.2008.09.050","article-title":"Stochastic gene expression and its consequences","volume":"135","author":"A Raj","year":"2008","journal-title":"Cell"},{"issue":"7194","key":"pcbi.1009811.ref005","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/nature06965","article-title":"Transcriptome-wide noise controls lineage choice in mammalian progenitor cells","volume":"453","author":"HH Chang","year":"2008","journal-title":"Nature"},{"issue":"12","key":"pcbi.1009811.ref006","doi-asserted-by":"crossref","first-page":"e2000640","DOI":"10.1371\/journal.pbio.2000640","article-title":"Cell Fate Decision as High-Dimensional Critical State Transition","volume":"14","author":"M Mojtahedi","year":"2016","journal-title":"PLOS Biol"},{"key":"pcbi.1009811.ref007","volume-title":"Current Protocols in Molecular Biology","author":"JD Buenrostro","year":"2001"},{"issue":"2","key":"pcbi.1009811.ref008","doi-asserted-by":"crossref","DOI":"10.1101\/pdb.prot5384","article-title":"DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells","volume":"2010","author":"L Song","year":"2010","journal-title":"Cold Spring Harb Protoc"},{"issue":"6","key":"pcbi.1009811.ref009","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1101\/gr.5533506","article-title":"FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin","volume":"17","author":"PG Giresi","year":"2007","journal-title":"Genome Res"},{"issue":"1","key":"pcbi.1009811.ref010","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.molcel.2015.11.003","article-title":"A Multiplexed System for Quantitative Comparisons of Chromatin Landscapes","volume":"61","author":"Viny AD Galen P van","year":"2016","journal-title":"Mol Cell"},{"issue":"10","key":"pcbi.1009811.ref011","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/nmeth.3542","article-title":"ChIPmentation: fast, robust, low-input ChIP-seq for histones and transcription factors.","volume":"12","author":"C Schmidl","year":"2015","journal-title":"Nat Methods"},{"key":"pcbi.1009811.ref012","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/978-1-61779-316-5_2","article-title":"DNA methylation detection: Bisulfite genomic sequencing analysis","volume":"791","author":"Y Li","year":"2011","journal-title":"Methods Mol Biol Clifton NJ"},{"issue":"4","key":"pcbi.1009811.ref013","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.cell.2012.10.009","article-title":"Nucleosomal Elements that Control the Topography of the Barrier to Transcription","volume":"151","author":"L Bintu","year":"2012","journal-title":"Cell"},{"issue":"11","key":"pcbi.1009811.ref014","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1140\/epje\/i2017-11596-2","article-title":"The role of DNA sequence in nucleosome breathing","volume":"40","author":"J Culkin","year":"2017","journal-title":"Eur Phys J E Soft Matter"},{"key":"pcbi.1009811.ref015","article-title":"Histone tails cooperate to control the breathing of genomic nucleosomes","author":"J Huertas","year":"2020","journal-title":"bioRxiv."},{"issue":"5940","key":"pcbi.1009811.ref016","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1126\/science.1172926","article-title":"Nucleosomal Fluctuations Govern the Transcription Dynamics of RNA Polymerase II","volume":"325","author":"C Hodges","year":"2009","journal-title":"Science"},{"issue":"48","key":"pcbi.1009811.ref017","doi-asserted-by":"crossref","first-page":"14840","DOI":"10.1073\/pnas.1506760112","article-title":"Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing","volume":"112","author":"S Jimeno-Gonz\u00e1lez","year":"2015","journal-title":"Proc Natl Acad Sci"},{"key":"pcbi.1009811.ref018","doi-asserted-by":"crossref","first-page":"e02407","DOI":"10.7554\/eLife.02407","article-title":"Genome-wide dynamics of Pol II elongation and its interplay with promoter proximal pausing, chromatin, and exons","volume":"3","author":"I Jonkers","year":"2014","journal-title":"eLife"},{"issue":"6","key":"pcbi.1009811.ref019","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1101\/gr.171405.113","article-title":"Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications","volume":"24","author":"A Veloso","year":"2014","journal-title":"Genome Res"},{"key":"pcbi.1009811.ref020","unstructured":"Wang L, Stein L, Ware D. The relationships among GC content, nucleosome occupancy, and exon size. ArXiv14042487 Q-Bio [Internet]. 2014 May 27 [cited 2021 Nov 5]; Available from: http:\/\/arxiv.org\/abs\/1404.2487"},{"issue":"1","key":"pcbi.1009811.ref021","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13072-017-0125-5","article-title":"Links between DNA methylation and nucleosome occupancy in the human genome","volume":"10","author":"CK Collings","year":"2017","journal-title":"Epigenetics Chromatin"},{"issue":"5","key":"pcbi.1009811.ref022","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1093\/nar\/gks893","article-title":"Effects of DNA methylation on nucleosome stability","volume":"41","author":"CK Collings","year":"2013","journal-title":"Nucleic Acids Res"},{"issue":"1\u20132","key":"pcbi.1009811.ref023","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.mrfmmm.2006.05.040","article-title":"Transcription Through Chromatin by RNA polymerase II: Histone Displacement and Exchange","volume":"618","author":"OI Kulaeva","year":"2007","journal-title":"Mutat Res"},{"issue":"12","key":"pcbi.1009811.ref024","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1038\/nsmb.2164","article-title":"The elongation rate of RNA polymerase determines the fate of transcribed nucleosomes","volume":"18","author":"L Bintu","year":"2011","journal-title":"Nat Struct Mol Biol"},{"issue":"13","key":"pcbi.1009811.ref025","doi-asserted-by":"crossref","first-page":"7623","DOI":"10.1093\/nar\/gkx513","article-title":"Crowding-induced transcriptional bursts dictate polymerase and nucleosome density profiles along genes","volume":"45","author":"AA van den Berg","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1009811.ref026","doi-asserted-by":"crossref","first-page":"e13051","DOI":"10.7554\/eLife.13051","article-title":"A continuum model of transcriptional bursting","volume":"5","author":"AM Corrigan","year":"2016","journal-title":"eLife"},{"issue":"10","key":"pcbi.1009811.ref027","doi-asserted-by":"crossref","first-page":"e1004292","DOI":"10.1371\/journal.pcbi.1004292","article-title":"Transcriptional Bursting in Gene Expression: Analytical Results for General Stochastic Models","volume":"11","author":"N Kumar","year":"2015","journal-title":"PLOS Comput Biol"},{"issue":"7","key":"pcbi.1009811.ref028","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000109","article-title":"The Generation of Promoter-Mediated Transcriptional Noise in Bacteria","volume":"4","author":"N Mitarai","year":"2008","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1009811.ref029","volume-title":"Stochastic Transport in Complex Systems: From Molecules to Vehicles","author":"A Schadschneider","year":"2011"},{"issue":"1","key":"pcbi.1009811.ref030","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1103\/RevModPhys.85.135","article-title":"Stochastic models of intracellular transport","volume":"85","author":"PC Bressloff","year":"2013","journal-title":"Rev Mod Phys."},{"issue":"3","key":"pcbi.1009811.ref031","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/BF01050430","article-title":"An exact solution of a one-dimensional asymmetric exclusion model with open boundaries","volume":"69","author":"B Derrida","year":"1992","journal-title":"J Stat Phys"},{"issue":"7","key":"pcbi.1009811.ref032","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1088\/0305-4470\/26\/7\/011","article-title":"Exact solution of a 1D asymmetric exclusion model using a matrix formulation","volume":"26","author":"B Derrida","year":"1993","journal-title":"J Phys Math Gen"},{"issue":"5","key":"pcbi.1009811.ref033","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1007\/BF01052811","article-title":"Exact solution of the totally asymmetric simple exclusion process: Shock profiles","volume":"73","author":"B Derrida","year":"1993","journal-title":"J Stat Phys"},{"issue":"6","key":"pcbi.1009811.ref034","doi-asserted-by":"crossref","first-page":"065002","DOI":"10.1088\/1751-8121\/aafb8a","article-title":"Totally asymmetric exclusion process with site-wise dynamic disorder","volume":"52","author":"B Waclaw","year":"2019","journal-title":"J Phys Math Theor"},{"issue":"30","key":"pcbi.1009811.ref035","doi-asserted-by":"crossref","first-page":"14995","DOI":"10.1073\/pnas.1903549116","article-title":"Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic","volume":"116","author":"J Cholewa-Waclaw","year":"2019","journal-title":"Proc Natl Acad Sci"},{"key":"pcbi.1009811.ref036","doi-asserted-by":"crossref","first-page":"123356","DOI":"10.1016\/j.physa.2019.123356","article-title":"Two-channel totally asymmetric simple exclusion process with site-wise dynamic disorder","volume":"545","author":"S Garg","year":"2020","journal-title":"Phys Stat Mech Its Appl"},{"key":"pcbi.1009811.ref037","volume-title":"Finite Markov Chains: With a New Appendix \u201cGeneralization of a Fundamental Matrix","author":"JG Kemeny","year":"1976"},{"issue":"2","key":"pcbi.1009811.ref038","doi-asserted-by":"crossref","first-page":"420","DOI":"10.2307\/3213413","article-title":"The Variance of Duration of Stay in an Absorbing Markov Process","volume":"15","author":"PF Rust","year":"1978","journal-title":"J Appl Probab"},{"key":"pcbi.1009811.ref039","article-title":"Mean and variance of first passage time in Markov chains with unknown parameters","author":"C Hernandez-Suarez","year":"2019","journal-title":"ArXiv190207789 Q-Bio Stat"},{"issue":"25","key":"pcbi.1009811.ref040","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/j100540a008","article-title":"Exact stochastic simulation of coupled chemical reactions","volume":"81","author":"DT Gillespie","year":"1977","journal-title":"J Phys Chem"},{"issue":"15","key":"pcbi.1009811.ref041","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1101\/gad.194936.112","article-title":"Transcription initiation by human RNA polymerase II visualized at single-molecule resolution","volume":"26","author":"A Revyakin","year":"2012","journal-title":"Genes Dev"},{"issue":"4","key":"pcbi.1009811.ref042","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/nar\/25.4.787","article-title":"RNA polymerase II stalled at a thymine dimer: footprint and effect on excision repair","volume":"25","author":"CP Selby","year":"1997","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"pcbi.1009811.ref043","doi-asserted-by":"crossref","first-page":"493","DOI":"10.4161\/nucl.22168","article-title":"Nucleosome spacing and chromatin higher-order folding","volume":"3","author":"SA Grigoryev","year":"2012","journal-title":"Nucleus"},{"issue":"12","key":"pcbi.1009811.ref044","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/embor.2011.196","article-title":"Fast transcription rates of RNA polymerase II in human cells","volume":"12","author":"P Maiuri","year":"2011","journal-title":"EMBO Rep"},{"issue":"1","key":"pcbi.1009811.ref045","doi-asserted-by":"crossref","first-page":"012106","DOI":"10.1103\/PhysRevE.97.012106","article-title":"Theoretical analysis of the distribution of isolated particles in totally asymmetric exclusion processes: Application to mRNA translation rate estimation","volume":"97","author":"K Dao Duc","year":"2018","journal-title":"Phys Rev E"},{"issue":"2","key":"pcbi.1009811.ref046","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.cels.2019.12.003","article-title":"The Key Parameters that Govern Translation Efficiency","volume":"10","author":"DD Erdmann-Pham","year":"2020","journal-title":"Cell Syst"},{"issue":"1","key":"pcbi.1009811.ref047","doi-asserted-by":"crossref","first-page":"e1007166","DOI":"10.1371\/journal.pgen.1007166","article-title":"The impact of ribosomal interference, codon usage, and exit tunnel interactions on translation elongation rate variation","volume":"14","author":"KD Duc","year":"2018","journal-title":"PLOS Genet"},{"key":"pcbi.1009811.ref048","first-page":"147017","article-title":"Theoretical quantification of interference in the TASEP: application to mRNA translation shows near-optimality of termination rates","author":"KD Duc","year":"2017","journal-title":"bioRxiv"},{"key":"pcbi.1009811.ref049","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4614-3615-7","volume-title":"Essentials of Stochastic Processes","author":"R. Durrett","year":"2012"},{"key":"pcbi.1009811.ref050","doi-asserted-by":"crossref","DOI":"10.1201\/b12537","volume-title":"An Introduction to Stochastic Processes with Applications to Biology","author":"LJS Allen","year":"2010"},{"issue":"2","key":"pcbi.1009811.ref051","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10955-011-0183-1","article-title":"Modeling Translation in Protein Synthesis with TASEP: A Tutorial and Recent Developments","volume":"144","author":"RKP Zia","year":"2011","journal-title":"J Stat Phys"},{"key":"pcbi.1009811.ref052","article-title":"Hydrodynamic Limit of the Inhomogeneous L-TASEP with Open Boundaries: Derivation and Solution","author":"DD Erdmann-Pham","year":"2018","journal-title":"ArXiv180305609 Cond-Mat Physicsmath-Ph"},{"issue":"12","key":"pcbi.1009811.ref053","doi-asserted-by":"crossref","first-page":"P12013","DOI":"10.1088\/1742-5468\/2014\/12\/P12013","article-title":"Dynamics of non-Markovian exclusion processes","volume":"2014","author":"D Khoromskaia","year":"2014","journal-title":"J Stat Mech Theory Exp"},{"key":"pcbi.1009811.ref054","volume-title":"Mathematical Modeling in Systems Biology: An Introduction","author":"BP Ingalls","year":"2013"},{"key":"pcbi.1009811.ref055","volume-title":"Prentice-Hall international series in the physical and chemical engineering sciences","author":"HS Fogler","year":"1999"},{"issue":"7","key":"pcbi.1009811.ref056","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1039\/C7MB00154A","article-title":"What shapes eukaryotic transcriptional bursting?","volume":"13","author":"D Nicolas","year":"2017","journal-title":"Mol Biosyst"},{"key":"pcbi.1009811.ref057","article-title":"Theory of transcription bursting: Stochasticity in the transcription rates","author":"R. Murugan","year":"2019","journal-title":"bioRxiv."},{"issue":"5","key":"pcbi.1009811.ref058","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.bpj.2020.01.017","article-title":"A Mechanochemical Model of Transcriptional Bursting","volume":"118","author":"A Klindziuk","year":"2020","journal-title":"Biophys J"},{"issue":"2","key":"pcbi.1009811.ref059","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.cell.2014.05.038","article-title":"Mechanism of Transcriptional Bursting in Bacteria","volume":"158","author":"S Chong","year":"2014","journal-title":"Cell"},{"key":"pcbi.1009811.ref060","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.sbspro.2011.08.047","article-title":"Distance- and Time-headway Distribution for Totally Asymmetric Simple Exclusion Process","volume":"20","author":"P Hrab\u00e1k","year":"2011","journal-title":"Procedia\u2014Soc Behav Sci"},{"issue":"1","key":"pcbi.1009811.ref061","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/brv.12452","article-title":"Gene transcription in bursting: a unified mode for realizing accuracy and stochasticity","volume":"94","author":"Y Wang","year":"2019","journal-title":"Biol Rev"},{"issue":"6163","key":"pcbi.1009811.ref062","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1126\/science.1242975","article-title":"Genetic determinants and cellular constraints in noisy gene expression","volume":"342","author":"A Sanchez","year":"2013","journal-title":"Science"},{"issue":"1","key":"pcbi.1009811.ref063","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/ncomms12248","article-title":"A single-molecule view of transcription reveals convoys of RNA polymerases and multi-scale bursting","volume":"7","author":"K Tantale","year":"2016","journal-title":"Nat Commun"},{"issue":"12","key":"pcbi.1009811.ref064","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.1016\/j.jmb.2016.04.017","article-title":"Coupling of RNA polymerase II transcription elongation with pre-mRNA splicing","volume":"428","author":"T Saldi","year":"2016","journal-title":"J Mol Biol"},{"key":"pcbi.1009811.ref065","unstructured":"Gene Structure [Internet]. [cited 2020 Jan 26]. Available from: http:\/\/www.cshlp.org\/ghg5_all\/section\/gene.shtml"},{"issue":"1","key":"pcbi.1009811.ref066","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bbagrm.2012.08.015","article-title":"Mechanism of transcription through a nucleosome by RNA polymerase II","volume":"1829","author":"OI Kulaeva","year":"2013","journal-title":"Biochim Biophys Acta BBA\u2014Gene Regul Mech"},{"issue":"5","key":"pcbi.1009811.ref067","doi-asserted-by":"crossref","first-page":"211","DOI":"10.5483\/BMBRep.2018.51.5.053","article-title":"Histone tail cleavage as a novel epigenetic regulatory mechanism for gene expression","volume":"51","author":"S-J Yi","year":"2018","journal-title":"BMB Rep"},{"issue":"11","key":"pcbi.1009811.ref068","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0015442","article-title":"A Complete Set of Nascent Transcription Rates for Yeast Genes","volume":"5","author":"V Pelechano","year":"2010","journal-title":"PLoS ONE"},{"issue":"6","key":"pcbi.1009811.ref069","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/nsmb.3228","article-title":"BRD4 is a Histone Acetyltransferase that Evicts Nucleosomes from Chromatin","volume":"23","author":"BN Devaiah","year":"2016","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"pcbi.1009811.ref070","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s40659-017-0124-9","article-title":"BRD4 inhibition suppresses cell growth, migration and invasion of salivary adenoid cystic carcinoma","volume":"50","author":"L Wang","year":"2017","journal-title":"Biol Res"},{"issue":"1","key":"pcbi.1009811.ref071","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1177\/0394632015572070","article-title":"BRD4 promotes tumor growth and epithelial-mesenchymal transition in hepatocellular carcinoma","volume":"28","author":"P Zhang","year":"2015","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"47","key":"pcbi.1009811.ref072","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.1038\/onc.2013.162","article-title":"DNA methylation determines nucleosome occupancy in the 5\u2032-CpG islands of tumor suppressor genes","volume":"32","author":"A Portela","year":"2013","journal-title":"Oncogene"},{"issue":"6","key":"pcbi.1009811.ref073","doi-asserted-by":"crossref","first-page":"L1183","DOI":"10.1152\/ajplung.00224.2016","article-title":"BRD4 mediates NF-\u03baB-dependent epithelial-mesenchymal transition and pulmonary fibrosis via transcriptional elongation","volume":"311","author":"B Tian","year":"2016","journal-title":"Am J Physiol-Lung Cell Mol Physiol"},{"issue":"1","key":"pcbi.1009811.ref074","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s13059-019-1870-5","article-title":"Epigenetic modifications of histones in cancer","volume":"20","author":"Z Zhao","year":"2019","journal-title":"Genome Biol"},{"issue":"1","key":"pcbi.1009811.ref075","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/s41467-019-08381-0","article-title":"Promoter-proximal pausing mediated by the exon junction complex regulates splicing","volume":"10","author":"J Akhtar","year":"2019","journal-title":"Nat Commun"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1009811","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T13:45:16Z","timestamp":1645623916000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1009811"}},"subtitle":[],"editor":[{"given":"Alexandre V.","family":"Morozov","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2022,2,10]]},"references-count":75,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1009811","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,10]]}}}