Transcriptional Infidelity Promotes Heritable Phenotypic Change In A Bistable Gene Network

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.


The authors 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, they 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.



Citation:
"Transcriptional infidelity promotes heritable phenotypic change
in a bistable gene network."Gordon AJE, Halliday JA, Blankschien MD, Burns PA, Yatagai F, et al. (2009)
PLoS Biol 7(2): e1000044. doi:10.1371/journal.pbio.1000044

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Source

Plos Biology