Issue Date: September 10, 2007
Taking Control Of Transcription
A small-molecule mimic of a protein transcription factor has been used to manipulate only a subset of its natural counterpart's web of genomic targets (ACS Chem. Biol. 2007, 2, 561). The result suggests that similar "artificial transcription factors" could be programmed to control subsets of genomic targets—say, only those related to disease. Peter B. Dervan and coworkers at Caltech used a DNA-binding polyamide to disrupt the interaction between DNA and hypoxia-inducible factor (HIF-1). HIF-1 activates several genes that help cells adapt to oxygen deficiencies that arise during normal physiological processes and during cancer progression. The researchers found that the polyamide affects only a handful of genes normally turned on by HIF-1, namely those that match the polyamide's specific DNA-binding preferences. In contrast, small interfering RNAs targeted against HIF-1 affect the expression of every gene controlled by HIF-1. Therefore, polyamides programmed to bind specific HIF-1-induced genes might be used to modulate only a desired subset of HIF-1 effects, the authors note.
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