Functional Roles of Pulsing in Genetic Circuits
A fundamental problem in biology is to understand how genetic circuits implement core cellular functions. Time-lapse microscopy techniques are beginning to provide a direct view of circuit dynamics in individual living cells. Unexpectedly, we are discovering that key transcription and regulatory factors pulse on and off repeatedly, and often stochastically, even when cells are maintained in constant conditions. This type of spontaneous dynamic behavior is pervasive, appearing in diverse cell types from microbes to mammalian cells. Here, we review recent work showing how pulsing is generated and controlled by underlying regulatory circuits and how it provides critical capabilities to cells in stress response, signaling, and development. A major theme is the ability of pulsing to enable time-based regulation analogous to strategies used in engineered systems. Thus, pulsatile dynamics is emerging as a central, and still largely unexplored, layer of temporal organization in the cell.
Additional Information© 2013 American Association for the Advancement of Science. We thank M. Dunlop, J. Dworkin, N. Friedman, J. Garcia-Ojalvo, R. Kishony, G. Lahav, J. McKinney, R. Murray, R. Phillips, G. Suel, S. Tay, N. Wingreen, and members of the Elowitz lab including M. Budde, F. Ding, P. Li, J. Markson, and A. Rosenthal for critical comments and feedback. This work was supported by NIH grants R01 GM079771-06, R01 GM086793A, and P50GM068763; Defense Advanced Research Projects Agency Biochronicity program grant D12AP00025; and the Packard Foundation.
Accepted Version - nihms596211.pdf