Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network. Export

@article{citeulike:4091031, abstract = {Bistable epigenetic switches are fundamental for cell fate determination in unicellular and multicellular organisms. Regulatory proteins associated with bistable switches are often present in low numbers and subject to molecular noise. It is becoming clear that noise in gene expression can influence cell fate. Although the origins and consequences of noise have been studied, the stochastic and transient nature of RNA errors during transcription has not been considered in the origin or modeling of noise nor has the capacity for such transient errors in information transfer to generate heritable phenotypic change been discussed. We used a classic bistable memory module to monitor and capture transient RNA errors: the lac operon of Escherichia coli comprises an autocatalytic positive feedback loop producing a heritable all-or-none epigenetic switch that is sensitive to molecular noise. Using single-cell analysis, we show that the frequency of epigenetic switching from one expression state to the other is increased when the fidelity of RNA transcription is decreased due to error-prone RNA polymerases or to the absence of auxiliary RNA fidelity factors GreA and GreB (functional analogues of eukaryotic TFIIS). Therefore, transcription infidelity contributes to molecular noise and can effect heritable phenotypic change in genetically identical cells in the same environment. Whereas DNA errors allow genetic space to be explored, RNA errors may allow epigenetic or expression space to be sampled. Thus, RNA infidelity should also be considered in the heritable origin of altered or aberrant cell behaviour.}, author = {Gordon, Alasdair J. and Halliday, Jennifer A. and Blankschien, Matthew D. and Burns, Philip A. and Yatagai, Fumio and Herman, Christophe}, citeulike-article-id = {4091031}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pbio.1000044}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19243224}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19243224}, day = {24}, doi = {10.1371/journal.pbio.1000044}, issn = {1545-7885}, journal = {PLoS biology}, keywords = {bistable, epigenetics, gene, heritable, network, phenotype, switches}, month = {February}, number = {2}, pages = {e44+}, posted-at = {2009-11-06 10:45:44}, priority = {2}, title = {Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network.}, url = {http://dx.doi.org/10.1371/journal.pbio.1000044}, volume = {7}, year = {2009} }

TY - JOUR ID - citeulike:4091031 L3 - citeulike-article-id:4091031 N2 - Bistable epigenetic switches are fundamental for cell fate determination in unicellular and multicellular organisms. Regulatory proteins associated with bistable switches are often present in low numbers and subject to molecular noise. It is becoming clear that noise in gene expression can influence cell fate. Although the origins and consequences of noise have been studied, the stochastic and transient nature of RNA errors during transcription has not been considered in the origin or modeling of noise nor has the capacity for such transient errors in information transfer to generate heritable phenotypic change been discussed. We used a classic bistable memory module to monitor and capture transient RNA errors: the lac operon of Escherichia coli comprises an autocatalytic positive feedback loop producing a heritable all-or-none epigenetic switch that is sensitive to molecular noise. Using single-cell analysis, we show that the frequency of epigenetic switching from one expression state to the other is increased when the fidelity of RNA transcription is decreased due to error-prone RNA polymerases or to the absence of auxiliary RNA fidelity factors GreA and GreB (functional analogues of eukaryotic TFIIS). Therefore, transcription infidelity contributes to molecular noise and can effect heritable phenotypic change in genetically identical cells in the same environment. Whereas DNA errors allow genetic space to be explored, RNA errors may allow epigenetic or expression space to be sampled. Thus, RNA infidelity should also be considered in the heritable origin of altered or aberrant cell behaviour. IS - 2 JF - PLoS biology SN - 1545-7885 TI - Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network. VL - 7 SP - e44 KW - bistable KW - epigenetics KW - gene KW - heritable KW - network KW - phenotype KW - switches AU - Gordon, Alasdair AU - Halliday, Jennifer AU - Blankschien, Matthew AU - Burns, Philip AU - Yatagai, Fumio AU - Herman, Christophe PY - 2009/02/24/ UR - http://dx.doi.org/10.1371/journal.pbio.1000044 ER -