Protein Dimerization Generates Bistability in Positive Feedback Loops
Chieh Hsu3, Vincent Jaquet3, Mumun Gencoglu, Attila Becskei correspondence email
Publication stage: In Press Corrected Proof
•RNA stem loops tune translation rates over two orders of magnitude
•Positive feedback loops with reduced translation generate bistable cell fates
•Dimerizing transcription factors generate bistability without cooperative binding
Bistability plays an important role in cellular memory and cell-fate determination. A positive feedback loop can generate bistability if it contains ultrasensitive molecular reactions. It is often difficult to detect bistability based on such molecular mechanisms due to its intricate interaction with cellular growth. We constructed transcriptional feedback loops in yeast. To eliminate growth alterations, we reduced the protein levels of the transcription factors by tuning the translation rates over two orders of magnitude with designed RNA stem loops. We modulated two ultrasensitive reactions, homodimerization and the cooperative binding of the transcription factor to the promoter. Either of them is sufficient to generate bistability on its own, and when acting together, a particularly robust bistability emerges. This bistability persists even in the presence of a negative feedback loop. Given that protein homodimerization is ubiquitous, it is likely to play a major role in the behavior of regulatory networks.
Received: September 24, 2015; Received in revised form: May 22, 2016; Accepted: June 16, 2016; Published: July 14, 2016
© 2016 The Author(s). Published by Elsevier Inc.
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