Making cellular memories

Abstract

The induction of a protracted response to a brief stimulus is a form of cellular memory. Here we describe the role of transcriptional regulation in both natural and synthetic memory networks and discuss the potential applications of engineered memory networks in medicine and industrial biotechnology.

Figure 1

Figure 1a. Dynamics of regulated gene circuits described by Hill functions. (i) The concentration of product Y is plotted as a function of the concentration of activator X, as described by Hill functions with n = 1, 2, and 4. β is the maximal expression level from Y’s promoter when X is bound, and K defines the concentration of X needed to reach the threshold for activation of Y (ii) The concentration of product Y is plotted as a function of the concentration of repressor X, as described by Hill functions with n = 1, 2, and 4. β is the maximal expression level from Y’s promoter when X is unbound, and K defines the concentration of X need to the threshold for repression of Y. Figure 1b. Network motifs that achieve biological memory: (i) positive feedback, (ii) double-negative feedback, and (iii) double-positive feedback.

Figure 1

Figure 1a. Dynamics of regulated gene circuits described by Hill functions. (i) The concentration of product Y is plotted as a function of the concentration of activator X, as described by Hill functions with n = 1, 2, and 4. β is the maximal expression level from Y’s promoter when X is bound, and K defines the concentration of X needed to reach the threshold for activation of Y (ii) The concentration of product Y is plotted as a function of the concentration of repressor X, as described by Hill functions with n = 1, 2, and 4. β is the maximal expression level from Y’s promoter when X is unbound, and K defines the concentration of X need to the threshold for repression of Y. Figure 1b. Network motifs that achieve biological memory: (i) positive feedback, (ii) double-negative feedback, and (iii) double-positive feedback.

Figure 2. Natural mechanisms of memory

(a) The phage lambda system switches between two states based on a mutual repression loop between lambda repressor and Cro (Ptashne, 2004). (b) Replication-coupled nucleosome assembly maintains silent chromatin. Some silent nucleosomes (red) contain (H3-H4)₂ tetramers (gray) with H3-K9Me methylation marks (yellow). Positive feedback can arise if newly synthesized nucleosomes (green) become methylated by histone methyltransferases bound to HP1 (blue) on adjacent nucleosomes, allowing methylated regions to persist through DNA replication and cell division (adapted from Vermaak, et al., 2003). (c) Positive-feedback-based, bistable networks govern Xenopus oocyte maturation (adpated from Xiong, et al., 2003). (d) Information storage in the brain is believed to involve bistable feedback networks (Ogasawara, et al., 2009).