Protein dimerization generates bistability in positive feedback loops

Hsu, Chieh and Jaquet, Vincent and Gencoglu, Mumun and Becskei, Attila (2016) Protein dimerization generates bistability in positive feedback loops. Cell reports, 16 (5). pp. 1204-1210. ISSN 2211-1247. (doi:https://doi.org/10.1016/j.celrep.2016.06.072) (Full text available)

PDF - Publisher pdf

Creative Commons Licence
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Download (766kB) Preview
[img]
Preview
Official URL
http://dx.doi.org/10.1016/j.celrep.2016.06.072

Abstract

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. Since protein homodimerization is ubiquitous, it is likely to play a major role in the behavior of regulatory networks.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH324.2 Computational biology
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Chieh Hsu
Date Deposited: 17 Jun 2016 08:01 UTC
Last Modified: 31 Aug 2016 14:57 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/55964 (The current URI for this page, for reference purposes)
Hsu, Chieh: https://orcid.org/0000-0002-4780-1222
  • Depositors only (login required):

Downloads

Downloads per month over past year