| Autor: |
Dar, Roy D, Hosmane, Nina N, Arkin, Michelle R, Siliciano, Robert F, Weinberger, Leor S |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Science (New York, N.Y.), vol 344, iss 6190 |
| Popis: |
Stochastic fluctuations are inherent to gene expression and can drive cell-fate specification. We used such fluctuations to modulate reactivation of HIV from latency-a quiescent state that is a major barrier to an HIV cure. By screening a diverse library of bioactive small molecules, we identified more than 80 compounds that modulated HIV gene-expression fluctuations (i.e., "noise"), without changing mean expression. These noise-modulating compounds would be neglected in conventional screens, and yet, they synergized with conventional transcriptional activators. Noise enhancers reactivated latent cells significantly better than existing best-in-class reactivation drug combinations (and with reduced off-target cytotoxicity), whereas noise suppressors stabilized latency. Noise-modulating chemicals may provide novel probes for the physiological consequences of noise and an unexplored axis for drug discovery, allowing enhanced control over diverse cell-fate decisions. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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