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Mapping the architecture of the HIV-1 Tat circuit: A decision-making circuit that lacks bistability and exploits stochastic noise
Ist Teil von
Methods (San Diego, Calif.), 2011, Vol.53 (1), p.68-77
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2011
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Upon infection of a CD4
+ T cell, HIV-1 appears to ‘choose’ between two alternate fates: active replication or a long-lived dormant state termed proviral latency. A transcriptional positive-feedback loop generated by the HIV-1 Tat protein appears sufficient to mediate this decision. Here, we describe a coupled wet-lab and computational approach that uses mathematical modeling and live-cell time-lapse microscopy to map the architecture of the HIV-1 Tat transcriptional regulatory circuit and generate predictive models of HIV-1 latency. This approach provided the first characterization of a ‘decision-making’ circuit that lacks bistability and instead exploits stochastic fluctuations in cellular molecules (i.e. noise) to generate a decision between an
on or
off transcriptional state.