Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 11 May 2004
Vol. 2004, Issue 232, p. pe20
[DOI: 10.1126/stke.2322004pe20]

PERSPECTIVES

Hysteresis vs. Graded Responses: The Connections Make All the Difference

Alexander J. Ninfa1* and Avraham E. Mayo2

1Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
2Departments of Molecular Cell Biology and Physics of Complex Systems, The Weizman Institute of Science, Rehovot 76100, Israel.

Summary: Biological regulatory systems have the potential to provide graded responses to stimuli or may demonstrate switch-like properties. Our understanding of the system design principles controlling these responses is still at a rudimentary stage, and here we consider several recent experimental and theoretical studies that focus on these system design principles. Overt positive feedback loops, or double-negative feedback loops, can produce bistable or multistable systems under the appropriate conditions and can produce graded responses under other conditions. Several design features favor bistability in negatively controlled genetic systems, including a high kinetic order for repression and a large difference in the rates of gene expression in the "on" and "off" states. In positive feedback, a high kinetic order for the activation of gene expression favors bistability. Multistability can result from the combined effects of positive and negative regulators, or from the combined effects of regulators that each demonstrate bistability. Finally, bistability can result in enzymatic systems in which multiple reversible covalent modifications occur, even when no overt feedback loops are present.

*Corresponding author. E-mail: aninfa{at}umich.edu

Citation: A. J. Ninfa, A. E. Mayo, Hysteresis vs. Graded Responses: The Connections Make All the Difference. Sci. STKE 2004, pe20 (2004).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Bistable switches control memory and plasticity in cellular differentiation.
L. Wang, B. L. Walker, S. Iannaccone, D. Bhatt, P. J. Kennedy, and W. T. Tse (2009)
PNAS 106, 6638-6643
   Abstract »    Full Text »    PDF »
Regulatory circuit based on autogenous activation-repression: roles of C-boxes and spacer sequences in control of the PvuII restriction-modification system.
I. Mruk, P. Rajesh, and R. M. Blumenthal (2007)
Nucleic Acids Res. 35, 6935-6952
   Abstract »    Full Text »    PDF »
Hysteresis in a synthetic mammalian gene network.
B. P. Kramer and M. Fussenegger (2005)
PNAS 102, 9517-9522
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882