Cells have several ways of ensuring that their daughters “remember” what kind of cells they are. One of the simplest and most important is through a positive feedback loop, where a master cell-type transcription regulator activates transcription of its own gene, in addition to that of other cell-type-specific genes. Each time a cell divides, the regulator is distributed to both daughter cells, where it continues to stimulate the positive feedback loop, making more of itself each division. Positive feedback is crucial for establishing “self-sustaining” circuits of gene expression that allow a cell to commit to a particular fate—and then to transmit that information to its progeny (Figure 7–39).
As was previously shown in Figure 7–37B, the master regulators needed to maintain the pluripotency of iPS cells bind to cis-regulatory sequences in their own control regions, providing examples of the type of positive feedback loop. In addition, most of these pluripotent cell regulators also activate transcription of other master regulators, resulting in a complex series of indirect feedback loops. For example, if A activates B, and B activates A, this forms a positive feedback loop where A activates its own expression, albeit indirectly. The series of direct and indirect feedback loops observed in the iPS circuit is typical of other specialized cell circuits. Such a network structure strengthens cell memory, increasing the probability that a particular pattern of gene expression is transmitted through successive generations. For example, if the level of A drops below the critical threshold to stimulate its own synthesis, regulator B can rescue it. By successive application of this mechanism, a complex series of positive feedback loops among multiple transcription regulators can stably maintain a differentiated state through many cell divisions.
Figure 7–39 A positive feedback loop can create cell memory. protein A is a master transcription regulator that activates the transcription of its own gene—as well as other cell-type-specific genes (not shown). All of the descendants of the original cell will therefore “remember” that the progenitor cell had experienced a transient signal that initiated the production of protein A.
Positive feedback loops formed by transcription regulators are probably the most prevalent way of ensuring that daughter cells remember what kind of cells they are meant to be, and they are found in all species on Earth. For example, many bacteria and single-cell eukaryotes form different types of cells, and positive feedback loops lie at the heart of mechanisms that maintain their cell types through many rounds of cell division. Plants and animals also make extensive use of transcription feedback loops; as we shall discuss later in the chapter, they have additional, more specialized mechanisms for making cell memory even stronger. But first, we briefly consider how combinations of transcription regulators and cis-regulatory sequences can be combined to create useful logic devices for the cell.
transcription Circuits Allow the Cell to Carry Out logic Operations