Figure 7–36 A combination of transcription regulators can induce a differentiated cell to de-differentiate into a pluripotent cell. the artificial expression of a set of three genes, each of which encodes a transcription regulator, can reprogram a fibroblast into a pluripotent cell with embryonic stem (eS)-cell-like properties. like eS cells, such induced pluripotent stem (ipS) cells can proliferate indefinitely in culture and can be stimulated by appropriate extracellular signal molecules to differentiate into almost any cell type found in the body. transcription regulators such as Oct4, Sox2, and Klf4 are often called master transcription regulators because their expression is sufficient to trigger a change in cell identity.
apparatus, while nerve cells must make and assemble all the proteins needed to form dendrites and synapses. We have seen that these patterns of cell-type-specific expression are orchestrated by a combination of master transcription regulators. In many cases, these proteins bind directly to cis-regulatory sequences of the genes particular to that cell type. Thus, MyoD binds directly to cis-regulatory sequences located in the control regions of the muscle-specific genes. In other cases, the master regulators control the expression of “downstream” transcription regulators which, in turn, bind to the control regions of other cell-type-specific genes and control their synthesis.
The specification of a particular cell type typically involves changes in the expression of several thousand genes. Genes whose protein products are required in the cell type are expressed at high levels, while those not needed are typically down-regulated. As might be imagined, the pattern of binding between the master regulators and all of the regulated genes can be extremely elaborate (Figure 7–37). When we consider that many of these regulated genes have control regions that span tens of thousands of nucleotide pairs, commensurate with the Eve example discussed above, we can begin to appreciate the enormous complexity of cell-type specification.
An outstanding question in biology is how the information in a genome is used to specify a multicellular organism. Although we have the general outline of the answer, we are far from understanding how a single cell type is completely specified, let alone a whole organism.
Specialized Cells Must rapidly turn Sets of Genes On and Off
Although they generally maintain their identities, specialized cells must constantly respond to changes in their environment. Among the most important changes are signals from other cells that coordinate the behavior of the whole organism. Many of these signals induce transient changes in gene transcription, and we discuss the nature of these signals in detail in Chapter 15. Here, we consider how specialized cell types rapidly and decisively switch groups of genes on and off in response to their environment. Even though control of gene expression is combinatorial, the effect of a single transcription regulator can still be decisive in switching any particular gene on or off, simply by completing the combination needed to maximally activate or repress that gene. This situation is analogous to dialing in the final number of a combination lock: the lock will spring open with only this simple addition if all of the other numbers have been previously entered.
Figure 7–37 A portion of the transcription network specifying embryonic stem cells. (A) the three master transcription regulators in figure 7–36 are shown as large circles. Genes whose cis-regulatory sequences are bound by each regulator in embryonic stem cells are indicated by a small dot (representing the gene) connected by a thin line (representing the binding reaction). note that many of the target genes are bound  by more than one of the regulators.
(B) the master regulators control their own expression. As shown here, the three transcriptional regulators bind to their own control regions (indicated by feedback loops), as well as those of the other master regulators (indicated by straight arrows). (Courtesy of trevor Sorrells, based on data from J. Kim et al., Cell 132:1049– 1061, 2008.)
Moreover, the same number can complete the combination for many different locks. Likewise, the addition of a particular protein can turn on many different genes.