For most genes, transcriptional controls are paramount. This makes sense because, of all the possible control points illustrated in Figure 7–5, only transcriptional control ensures that the cell will not synthesize superfluous intermediates. In the following sections, we discuss the DNA and protein components that perform this function by regulating the initiation of gene transcription. We shall then return to the additional ways of regulating gene expression.
Figure 7–4 Differences in the proteins expressed by two human tissues, (A) brain and (B) liver. in each panel, the proteins are displayed using two-dimensional polyacrylamide-gel electrophoresis (see pp. 452–454). the proteins have been separated by molecular weight (top to bottom) and isoelectric point, the ph at which the protein has no net charge (right to left). the protein spots artificially colored red are common to both samples; those in blue are specific to that tissue. the differences between the two tissue samples vastly outweigh their similarities: even for proteins that are shared between the two tissues, their relative abundances are usually different. note that this technique separates proteins by both size and charge; therefore a protein that has several different phosphorylation states will appear as a series of horizontal spots (see upper right-hand portion of right panel). Only a small portion of the complete protein spectrum is shown for each sample.
Methods based on mass spectrometry (see pp. 455–457) provide much more detailed information, including the identity of each protein, the position of each modification, and the nature of the modification. (Courtesy of tim Myers and leigh Anderson, large Scale Biology Corporation.)
The genome of a cell contains in its DNA sequence the information to make many thousands of different protein and RNA molecules. A cell typically expresses only a fraction of its genes, and the different types of cells in multicellular organisms arise because different sets of genes are expressed. Moreover, cells can change the pattern of genes they express in response to changes in their environment, such as signals from other cells. Although all of the steps involved in expressing a gene can in principle be regulated, for most genes the initiation of RNA transcription provides the most important point of control.
How does a cell determine which of its thousands of genes to transcribe? Perhaps the most important concept, one that applies to all species on Earth, is based on a group of proteins known as transcription regulators. These proteins recognize specific sequences of DNA (typically 5–10 nucleotide pairs in length) that are often called cis-regulatory sequences, because they must be on the same chromosome (that is, in cis) to the genes they control. Transcription regulators bind to these sequences, which are dispersed throughout genomes, and this binding puts into motion a series of reactions that ultimately specify which genes are to be transcribed and at what rate. Approximately 10% of the protein-coding genes of most organisms are devoted to transcription regulators, making them one of the largest classes of proteins in the cell. In most cases, a given transcription regulator recognizes its own cis-regulatory sequence, which is different from those recognized by all the other regulators in the cell.
Transcription of each gene is, in turn, controlled by its own collection of cis-regulatory sequences. These typically lie near the gene, often in the intergenic region directly upstream from the transcription start point of the gene. Although a few genes are controlled by a single cis-regulatory sequence that is recognized by a single transcription regulator, the majority have complex arrangements of cis-regulatory sequences, each of which is recognized by a different transcription regulator. It is therefore the positions, identity, and arrangement of cis-regulatory sequences—which are an important part of the information embedded in the genome—that ultimately determine the time and place that each gene is transcribed.
We begin our discussion by describing how transcription regulators recognize cis-regulatory sequences.
the Sequence of nucleotides in the DnA Double helix Can Be read by proteins
As discussed in Chapter 4, the DNA in a chromosome consists of a very long double helix that has both a major and a minor groove (Figure 7–6). Transcription regulators must recognize short, specific cis-regulatory sequences within