“breathing” cis-regulatory sequence this open form occurs about 1/20th of the time (A) (B) compared to its affnity for naked DNA, a typical transcription regulator will bind with 20 times lower affnity if its cis-regulatory sequence is located near the end of a nucleosome a typical transcription regulator will bind with roughly 200-fold less affnity + + transcription regulatorhistone core + + + (C) if its cis-regulatory sequence is located in the middle of a nucleosome (D) one transcription regulator can destabilize the nucleosome, facilitating binding of another
The cooperation among transcription regulators can become much greater when nucleosome remodeling complexes are involved. If one transcription regulator binds its cis-regulatory sequence and attracts a chromatin remodeling complex, the localized action of the remodeling complex can allow a second transcription regulator to efficiently bind nearby. Moreover, we have discussed how transcription regulators can work together in pairs; in reality, larger numbers often cooperate by repeated use of the same principles. A highly cooperative binding of transcription regulators to DNA probably explains why many sites in eukaryotic genomes that are bound by transcription regulators are “nucleosome free.”
Transcription regulators recognize short stretches of double-helical DNA of defined sequence called cis-regulatory sequences, and thereby determine which of the thousands of genes in a cell will be transcribed. Approximately 10% of the protein-coding genes in most organisms produce transcription regulators, and they control many features of cells. Although each of these transcription regulators has unique features, most bind to DNA as homodimers or heterodimers and recognize DNA through one of a small number of structural motifs. Transcription regulators typically work in groups and bind DNA cooperatively, a feature that has several underlying mechanisms, some of which exploit the packaging of DNA in nucleosomes.
Having seen how transcription regulators bind to cis-regulatory sequences embedded in the genome, we can now discuss how, once bound, these proteins influence the transcription of genes. The situation in bacteria is simpler than in eukaryotes (for one thing, chromatin structure is not an issue), and we therefore discuss it first. Following this, we turn to the more complex situation in eukaryotes.
the tryptophan repressor Switches Genes Off
The genome of the bacterium E. coli consists of a single, circular DNA molecule of about 4.6 × 106 nucleotide pairs. This DNA encodes approximately 4300 proteins, although only a fraction of these are made at any one time. Bacteria regulate the expression of many of their genes according to the food sources that are available in the environment. For example, in E. coli, five genes code for enzymes that manufacture the amino acid tryptophan. These genes are arranged in a cluster on the chromosome and are transcribed from a single promoter as one long mRNA molecule; such coordinately transcribed clusters are called operons (Figure 7–12). Although operons are common in bacteria, they are rare in eukaryotes, where genes are typically transcribed and regulated individually (see Figure 7–3).
When tryptophan concentrations are low, the operon is transcribed; the resulting mRNA is translated to produce a full set of biosynthetic enzymes, which work in tandem to synthesize tryptophan from much simpler molecules. When tryptophan is abundant, however—for example, when the bacterium is in the gut of a mammal that has just eaten a protein-rich meal—the amino acid is imported into the cell and shuts down production of the enzymes, which are no longer needed.
E. coli chromosome series of enzymes required for tryptophan biosynthesis