In bacteria, gene control serves mainly to allow a single cell to adjust to changes in its environment so that its growth and division can be optimized. In multicellular organisms, environmental changes also induce changes in gene expression. An example is the response to low oxygen concentrations (hypoxia), in which a specific set of genes is rapidly induced that helps the cell survive under the hypoxic conditions. These genes include those encoding secreted angiogenic proteins that stimulate the growth and penetration of new capillaries into the surrounding tissue. However, the most characteristic and biologically far-reaching purpose of gene control in multicellular organisms is execution of the genetic program that underlies embryological development. Generation of the many different cell types that collectively form a multicellular organism depends on the right genes being activated in the right cells at the right time during the developmental period.
In most cases, once a developmental step has been taken by a cell, it is not reversed. Thus these decisions are fundamentally different from the reversible activation and repression of bacterial genes in response to environmental conditions. In executing their genetic programs, many differentiated cells (e.g., skin cells, red blood cells, and antibody-producing cells) march down a pathway to final cell death, leaving no progeny behind. The fixed patterns of gene control leading to differentiation serve the needs of the whole organism and not the survival of an individual cell.
Despite the differences in the purposes of gene control in bacteria and eukaryotes, two key features of transcriptional control first discovered in bacteria and described in the previous section also apply to eukaryotic cells. First, protein-binding regulatory DNA sequences, or transcription-control regions, are associated with genes. Second, specific proteins that bind to a gene’s transcription-control regions determine where transcription will start and either activate or repress transcription. One fundamental difference between transcriptional control in bacteria and in eukaryotes is a consequence of the association of eukaryotic chromosomal DNA with histone octamers, forming nucleosomes that associate into chromatin fibers that further associate into chromatin of varying degrees of condensation (see Figures 8-24, 8-25, 8-27, and 8-28). Eukaryotic cells exploit chromatin structure to regulate transcription, a mechanism of transcriptional control that is not available to bacteria. In multicellular eukaryotes, many inactive genes are assembled into condensed chromatin, which inhibits binding of the RNA polymerases and general transcription factors required for transcription initiation (see Figure 9-3). Activator proteins, which bind to transcription-control regions near the transcription start site of a gene as well as kilobases away, promote chromatin decondensation, binding of RNA polymerase to the promoter, and transcriptional elongation. Repressor proteins, which bind to alternative control elements, cause condensation of chromatin and inhibition of polymerase binding or elongation. In this section, we discuss the general principles of eukaryotic gene control and point out some similarities and differences between bacterial and eukaryotic systems. Subsequent sections of this chapter will address specific aspects of eukaryotic transcription in greater detail.