A continuum model of transcriptional bursting

ELife
Adam M CorriganJonathan R Chubb

Abstract

Transcription occurs in stochastic bursts. Early models based upon RNA hybridisation studies suggest bursting dynamics arise from alternating inactive and permissive states. Here we investigate bursting mechanism in live cells by quantitative imaging of actin gene transcription, combined with molecular genetics, stochastic simulation and probabilistic modelling. In contrast to early models, our data indicate a continuum of transcriptional states, with a slowly fluctuating initiation rate converting the gene between different levels of activity, interspersed with extended periods of inactivity. We place an upper limit of 40 s on the lifetime of fluctuations in elongation rate, with initiation rate variations persisting an order of magnitude longer. TATA mutations reduce the accessibility of high activity states, leaving the lifetime of on- and off-states unchanged. A continuum or spectrum of gene states potentially enables a wide dynamic range for cell responses to stimuli.

References

May 9, 1998·Science·A M FeminoR H Singer
Nov 11, 1998·Molecular Cell·E BertrandR M Long
Jun 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·J PaulssonM Ehrenberg
May 29, 2004·Science·Jonathan M Raser, Erin K O'Shea
May 6, 2005·Nature·L EichingerA Kuspa
Dec 20, 2005·Cell·Ido GoldingEdward C Cox
May 23, 2006·Current Biology : CB·Ido Golding, Edward C Cox
May 23, 2006·Current Biology : CB·Jonathan R ChubbRobert H Singer
Oct 20, 2006·PLoS Biology·Arjun RajSanjay Tyagi
Aug 7, 2007·Nature Structural & Molecular Biology·Xavier DarzacqRobert H Singer
Oct 30, 2008·Cell·Arjun Raj, Alexander van Oudenaarden
Nov 18, 2008·Nature Structural & Molecular Biology·Daniel ZenklusenRobert H Singer
Nov 17, 2009·Nature Biotechnology·Rupali P PatwardhanJay Shendure
Jan 30, 2010·Development·Michelle StevenseJonathan R Chubb
Feb 5, 2010·Journal of Cell Science·Claire V HarperMichael R H White
Mar 2, 2010·Current Biology : CB·Tetsuya MuramotoJonathan R Chubb
Jul 20, 2010·Current Opinion in Genetics & Development·Jonathan R Chubb, Tanniemola B Liverpool
Aug 28, 2010·Current Biology : CB·Michael W PerryMichael Levine
Sep 11, 2010·Nature·Avigdor Eldar, Michael B Elowitz
Oct 22, 2011·EMBO Reports·Paolo MaiuriAlessandro Marcello
Apr 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tetsuya MuramotoJonathan R Chubb
Oct 16, 2012·Proceedings of the National Academy of Sciences of the United States of America·Roy D DarLeor S Weinberger
Mar 30, 2013·Nature Methods·Florian MuellerChristophe Zimmer
Oct 22, 2013·Current Biology : CB·Tanguy LucasNathalie Dostatni
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Nacho MolinaFélix Naef
Jan 7, 2014·Current Biology : CB·Adam M Corrigan, Jonathan R Chubb
Mar 13, 2014·Biophysical Journal·Georg Rieckh, Gašper Tkačik
Apr 20, 2014·Nucleic Acids Research·Andreas GietlDina Grohmann
May 9, 2014·Ecology·Ken AhoTeri Peterson
Jul 2, 2014·Cell Reports·Adrien SenecalXavier Darzacq
Jul 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jacques P BothmaMichael Levine
Jul 19, 2014·Cell·Shasha ChongX Sunney Xie
Jul 20, 2014·Molecular Cell·Zakary S SingerMichael B Elowitz
Mar 3, 2015·Molecular Cell·Keren Bahar HalpernShalev Itzkovitz

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Citations

Jun 14, 2016·Cell·Takashi FukayaMichael Levine
Jun 3, 2017·Molecular BioSystems·Damien NicolasFelix Naef
Jun 18, 2017·Nucleus·M HornáčekE Smirnov
Dec 1, 2017·Nature Reviews. Molecular Cell Biology·Ivan MarazziErnesto Guccione
Dec 31, 2017·The Journal of Cell Biology·Emily J PlattMathew J Thayer
Jul 20, 2018·Biological Reviews of the Cambridge Philosophical Society·Yaolai WangFeng Liu
Dec 30, 2017·Nucleus·Evgeny SmirnovIvan Raška
Jan 16, 2019·Investigative Ophthalmology & Visual Science·Saima LimiAles Cvekl
Mar 21, 2019·Development·Vlatka AntolovićJonathan R Chubb
Apr 6, 2019·Biological Chemistry·Chrysa NikopoulouPeter Tessarz
Feb 12, 2020·Molecular Systems Biology·Robert Foreman, Roy Wollman
Feb 23, 2020·Scientific Reports·Michael WilkinsonGreg Huber
Mar 27, 2020·Annual Review of Biochemistry·Joseph Rodriguez, Daniel R Larson
Jul 23, 2020·G3 : Genes - Genomes - Genetics·Eyal Metzl-RazNaama Barkai
Dec 16, 2016·PLoS Computational Biology·Jatin NarulaOleg A Igoshin
Jul 19, 2017·Wiley Interdisciplinary Reviews. Developmental Biology·Jonathan R Chubb
Oct 5, 2017·Nucleic Acids Research·Karen ClaußJ Christof M Gebhardt
Sep 8, 2016·Genes & Development·Huimin Chen, Daniel R Larson
Oct 5, 2017·Scientific Reports·Viola Vaňková Hausnerová, Christian Lanctôt
Sep 19, 2020·Physical Review. E·Gennady Gorin, Lior Pachter
Aug 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Edward TunnacliffeJonathan R Chubb
Mar 27, 2019·Communications Biology·Mona K TonnDiego A Oyarzún
Dec 29, 2019·Proceedings of the National Academy of Sciences of the United States of America·Nicholas C LammersHernan G Garcia
May 19, 2017·Nucleic Acids Research·Estelle DacheuxJohn E G McCarthy
Dec 10, 2020·Journal of Developmental Biology·Duncan WotherspoonRyan F L O'Shaughnessy
Aug 6, 2019·Developmental Cell·ChangHwan LeeJudith Kimble
Feb 12, 2021·The FEBS Journal·Ian S Hsu, Alan M Moses
Jan 12, 2020·Communications Biology·Mona K TonnDiego A Oyarzún
Feb 13, 2020·Biophysical Journal·Alena KlindziukAnatoly B Kolomeisky
Apr 25, 2021·Experimental Eye Research·Ales Cvekl, Carolina Eliscovich
Jun 2, 2021·Nucleic Acids Research·Achim P PoppJ Christof M Gebhardt
Nov 27, 2020·Current Opinion in Cell Biology·Nicholas C LammersHernan G Garcia
Jan 19, 2018·Cell Reports·Victor C WongKathryn Miller-Jensen
Jul 25, 2021·Nature Communications·Katjana TantaleEdouard Bertrand

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Methods Mentioned

BETA
smFISH
targeted mutations
fluorescence microscopy
fluorescence recovery after photobleaching
PCR

Software Mentioned

FISH
smFISH
MATLAB
quant

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