The stripe 2 element is autonomous, inasmuch as it specifies stripe 2 when isolated from its normal context (see Figure 7–28). The other stripe regulatory modules are thought to be constructed similarly, reading positional information provided by other combinations of transcription regulators. The entire Eve gene control region binds more than 20 different transcription regulators. Seven combinations of regulators—one combination for each stripe—specify Eve expression, while many other combinations (all those found in the interstripe regions of
Figure 7–29 The Eve stripe 2 unit. the segment of the Eve gene control region identified in figure 7–28 contains cisregulatory sequences for four transcription regulators. it is known from genetic experiments that these four regulatory proteins are responsible for the proper expression of Eve in stripe 2. flies that are deficient in the two gene activators Bicoid and hunchback, for example, fail to efficiently express Eve in stripe 2. in flies deficient in either of the two gene repressors, Giant and Krüppel, stripe 2 expands and covers an abnormally broad region of the embryo. As indicated, in some cases the binding sites for the transcription regulators overlap, and the proteins can compete for binding to the DnA. for example, binding of Krüppel and binding of Bicoid to the site at the far right is mutually exclusive.
the embryo) keep the stripe elements silent. A large and complex control region is thereby built from a series of smaller modules, each of which consists of a unique arrangement of short cis-regulatory sequences recognized by specific transcription regulators.
The Eve gene itself encodes a transcription regulator, which, after its pattern of expression is set up in seven stripes, controls the expression of other Drosophila genes. As development proceeds, the embryo is thus subdivided into finer and finer regions that eventually give rise to the different body parts of the adult fly, as discussed in Chapter 21.
Eve exemplifies the complex control regions found in plants and animals. As this example shows, control regions can respond to many different inputs, integrate this information, and produce a complex spatial and temporal output as development proceeds. However, exactly how all these mechanisms work together to produce the final output is understood only in broad outline (Figure 7–31).
The above example from Drosophila clearly illustrates the power of combinatorial control, but this case is unusual in that the nuclei are exposed directly to positional cues in the form of concentrations of transcription regulators. In embryos of most other organisms and in all adults, individual nuclei are in separate cells, and extracellular information (including positional cues) must be passed across the plasma membrane so as to generate signals in the cytosol that cause different transcription regulators to become active in different cell types. Some of the different mechanisms that are known to be used to activate transcription regulators are diagrammed in Figure 7–32, and in Chapter 15, we discuss how extracellular signals trigger these changes.
strongly activating assembly neutral assembly of
Figure 7–30 Distribution of the transcription regulators responsible for ensuring that Eve is expressed in stripe 2. the distributions of these proteins were visualized by staining a developing Drosophila embryo with antibodies directed against each of the four proteins. the expression of Eve in stripe 2 occurs only at the position where the two activators (Bicoid and hunchback) are present and the two repressors (Giant and Krüppel) are absent. in fly embryos that lack Krüppel, for example, stripe 2 expands posteriorly. likewise, stripe 2 expands posteriorly if the DnA-binding sites for Krüppel in the stripe 2 module are inactivated by mutation (see also figures 7–26 and 7–27).