Converting a eukaryotic transcriptional inhibitor into an activator

doi:10.1016/0092-8674(88)90030-X

Cell

Volume 55, Issue 3, 4 November 1988, Pages 443-446

https://doi.org/10.1016/0092-8674(88)90030-X Get rights and content

Abstract

GAL80, an inhibitor of the yeast transcriptional activator GAL4, is converted into an activator by inserting an acidic activating sequence into it. This hybrid activator does not bind to DNA directly, but is brought to DNA by interacting with a derivative of GAL4 that interacts with both DNA and GAL80.

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Citation Excerpt :
A prediction of these ideas was that attaching an activating region to Gal80 would turn it into an activator, so long as it could be tethered to DNA by interaction with Gal4. This turned out to be true (63). This result, which reinforced the idea that activating regions must be tethered to DNA to work, triggered development by others of the “two-hybrid” system (64).
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This synthetic approach could be utilized to explore the diversity of behaviors that can be programmed by even just a few transcriptional components; furthermore, our findings provide simple strategies for reprogramming the signal processing behavior of a cell. Similar strategies are undoubtedly employed naturally, where there are many examples of individual proteins that can take on either activating or repressing roles depending on the cellular and environmental states (Ma and Ptashne, 1988; Maxon and Herskowitz, 2001; Rubin-Bejerano et al., 1996). Given that TFs containing ZFs play a central role in eukaryotic promoter regulation (Pabo et al., 2001), our system represents a promising means for synthetic recapitulation of eukaryotic promoter function, and thus will significantly enhance our ability to construct synthetic gene networks in mammalian cells, an area of tremendous potential in synthetic biology (Weber and Fussenegger, 2009).
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We were consistently forced to revisit these elusive acceptor proteins when we realized that they were not only sufficient to promote NR activity but were required for optimal receptor activation. A further motivation to identify these acceptor proteins came when Ma and Ptashne published that yeast Gal80, an inhibitor of Gal4, could be transformed from a transcriptional repressor to an activator by inserting an acidic activating sequence (4). In 1991, studies followed in Drosophila showing that TATA-binding protein-associated factors interact through TATA-binding protein to regulate basal promoter activity (5).
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Cell

ArticleConverting a eukaryotic transcriptional inhibitor into an activator

Abstract

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Oncogene jun encodes a sequence-specific transactivator similar to AP-1

Nature

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Science

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Nature

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Article
Converting a eukaryotic transcriptional inhibitor into an activator