Open Access. Powered by Scholars. Published by Universities.®
Physical Sciences and Mathematics Commons™
Open Access. Powered by Scholars. Published by Universities.®
- Discipline
Articles 1 - 2 of 2
Full-Text Articles in Physical Sciences and Mathematics
Unraveling The Mechanism Of A Potent Transcriptional Activator, Brian Brennan, Zhen Lu, Steven Rowe, Sarah Davis, Renee Metzler, Johnathan Nau, Chinmay Majmudar, Anna Mapp, Aseem Ansari
Unraveling The Mechanism Of A Potent Transcriptional Activator, Brian Brennan, Zhen Lu, Steven Rowe, Sarah Davis, Renee Metzler, Johnathan Nau, Chinmay Majmudar, Anna Mapp, Aseem Ansari
Brian B. Brennan
Despite their enormous potential as novel research tools and therapeutic agents, artificial transcription factors (ATFs) that up-regulate transcription robustly in vivo remain elusive. In investigating an ATF that does function exceptionally well in vivo, we uncovered an unexpected relationship between transcription function and a binding interaction between the activation domain and an adjacent region of the DNA binding domain. Disruption of this interaction leads to complete loss of function in vivo, even though the activation domain is still able to bind to its target in the transcriptional machinery. We propose that this interaction parallels those between natural activation domains and …
Stereochemical Promiscuity In Artificial Transcriptional Activators, Brian Brennan, Sara Buhrlage, Aaron Minter, Anna Mapp
Stereochemical Promiscuity In Artificial Transcriptional Activators, Brian Brennan, Sara Buhrlage, Aaron Minter, Anna Mapp
Brian B. Brennan
Small molecule replacements of transcriptional activation domains are highly desirable targets due to their utility as mechanistic tools and their long-term therapeutic potential for a variety of human diseases. Here, we examine the ability of amphipathic isoxazolidines differing only in the placement of constituent side chains to function as transcriptional activation domains. The results reveal that precise positioning of functional groups within a conformationally constrained small molecule scaffold is not required for transcription function; rather, the balance of polarity and hydrophobicity within the scaffold is the more important determinant of transcription function. This suggests that a number of different organic …