Why are cellular switches Boolean? General conditions for multistable genetic circuits Export

@article{citeulike:5314141, abstract = {The logic of cellular decision-making is largely controlled by regulatory circuits defining molecular switches. Such switching elements allow to turn a graded input signal into an all-or-nothing output. Traditional studies have focused on this bistable picture of regulation, but higher-order scenarios involving tristable and tetrastable states are possible too. Are these multiswitches allowed in simple gene regulatory networks? Are they likely to be observed? If not, why not? In this paper we present the examination of this question by means of a simple but powerful geometric approach. We examine the relation between multistability, the degree of multimerization of the regulators and the role of autoloops within a deterministic setting, finding that N -stable circuits are possible, although their likelihood to occur rapidly decays with the order of the switch. Our work indicates that, despite two-component circuits are able to implement multistability, they are optimal for Boolean switches. The evolutionary implications are outlined.}, author = {Mac\'{\i}a, Javier and Widder, Stefanie and Sol\'{e}, Ricard}, citeulike-article-id = {5314141}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jtbi.2009.07.019}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0022519309003221}, day = {07}, doi = {10.1016/j.jtbi.2009.07.019}, issn = {00225193}, journal = {Journal of Theoretical Biology}, month = {November}, number = {1}, pages = {126--135}, posted-at = {2009-10-05 05:24:14}, priority = {2}, title = {Why are cellular switches Boolean? General conditions for multistable genetic circuits}, url = {http://dx.doi.org/10.1016/j.jtbi.2009.07.019}, volume = {261}, year = {2009} }

TY - JOUR ID - citeulike:5314141 L3 - citeulike-article-id:5314141 N2 - The logic of cellular decision-making is largely controlled by regulatory circuits defining molecular switches. Such switching elements allow to turn a graded input signal into an all-or-nothing output. Traditional studies have focused on this bistable picture of regulation, but higher-order scenarios involving tristable and tetrastable states are possible too. Are these multiswitches allowed in simple gene regulatory networks? Are they likely to be observed? If not, why not? In this paper we present the examination of this question by means of a simple but powerful geometric approach. We examine the relation between multistability, the degree of multimerization of the regulators and the role of autoloops within a deterministic setting, finding that N -stable circuits are possible, although their likelihood to occur rapidly decays with the order of the switch. Our work indicates that, despite two-component circuits are able to implement multistability, they are optimal for Boolean switches. The evolutionary implications are outlined. IS - 1 JF - Journal of Theoretical Biology SN - 00225193 EP - 135 TI - Why are cellular switches Boolean? General conditions for multistable genetic circuits VL - 261 SP - 126 AU - Macía, Javier AU - Widder, Stefanie AU - Solé, Ricard PY - 2009/11/07/ UR - http://dx.doi.org/10.1016/j.jtbi.2009.07.019 ER -