Figure 7–23 Six ways in which eukaryotic repressor proteins can operate. (A) Activator proteins and repressor proteins compete for binding to the same regulatory DnA sequence. (B) Both proteins bind DnA, but the repressor prevents the activator from carrying out its functions. (C) the repressor blocks assembly of the general transcription factors. (D) the repressor recruits a chromatin remodeling complex, which returns the nucleosomal state of the promoter region to its pre-transcriptional form. (e) the repressor attracts a histone deacetylase to the promoter. As we have seen, histone acetylation can stimulate transcription initiation (see figure 7–20), and the repressor simply reverses this modification. (f) the repressor attracts a histone methyl transferase, which modifies certain positions on histones by attaching methyl groups; the methylated histones, in turn, are bound by proteins that maintain the chromatin in a transcriptionally silent form.
repress the transcription of genes. These transcription repressors can both depress the rate of transcription below the default value and rapidly shut off genes that were previously activated. We saw in Chapter 4 that large regions of the genome can be shut down by the packaging of DNA into especially resistant forms of chromatin. However, eukaryotic genes are rarely organized along the genome according to function, and this strategy is not generally applicable for shutting off a set of genes that work together. Instead, most eukaryotic repressors work on a geneby-gene basis. Unlike bacterial repressors, eukaryotic repressors do not directly compete with the RNA polymerase for access to the DNA; rather, they use a variety of other mechanisms, some of which are illustrated in Figure 7–23. Although all of these mechanisms ultimately block transcription by RNA polymerase, eukaryotic transcription repressors typically act by bringing co-repressors to DNA. Like transcription activation, transcription repression can act through more than one mechanism at a given target gene, thereby ensuring especially efficient repression.
Gene repression is especially important to animals and plants whose growth depends on elaborate and complex developmental programs. Misexpression of a single gene at a critical time can have disastrous consequences for the individual. For this reason, many of the genes encoding the most important developmental regulatory proteins are kept tightly repressed when they are not needed.
sequence domain of actively
Figure 7–24 Schematic diagram summarizing the properties of insulators and barrier sequences. (A) insulators directionally block the action of cis-regulatory sequences, whereas barrier sequences prevent the spread of heterochromatin. how barrier sequences likely function is depicted in figure 4–41. (B) insulator-binding proteins (purple) hold chromatin in loops, thereby favoring “correct” cis-regulatory sequence–gene associations. thus, gene B is properly regulated, and gene B’s cisregulatory sequences are prevented from influencing the transcription of gene A.
We have seen that all genes have control regions, which dictate at which times, under what conditions, and in what tissues the gene will be expressed. We have also seen that eukaryotic transcription regulators can act across very long stretches of DNA, with the intervening DNA looped out. How, then, are control regions of different genes kept from interfering with one another? For example, what keeps a transcription regulator bound on the control region of one gene from looping in the wrong direction and inappropriately influencing the transcription of an adjacent gene?