The release of RNA polymerase can occur in several ways. In some cases, the activator brings in a chromatin remodeling complex that removes a nucleosome block to the elongating RNA polymerase. In other cases, the activator communicates with RNA polymerase (typically through a coactivator), signaling it to move ahead. Finally, as we saw in Chapter 6, RNA polymerase requires elongation factors to effectively transcribe through chromatin. In some cases, the key step in gene activation is the loading of these factors onto RNA polymerase, which can be directed by DNA-bound transcription activators. Once loaded, these factors allow the polymerase to move through blocks imposed by chromatin structure and begin transcribing the gene in earnest. Having RNA polymerase already poised on a promoter in the beginning stages of transcription bypasses the step of assembling many components at the promoter, which is often slow. This mechanism can therefore allow cells to begin transcribing a gene as a rapid response to an extracellular signal.
We have seen that complexes of transcription activators and coactivators assemble cooperatively on DNA. We have also seen that these assemblies can promote different steps in transcription initiation. In general, where several factors work together to enhance a reaction rate, the joint effect is not merely the sum of the enhancements that each factor alone contributes, but the product. If, for example, factor A lowers the free-energy barrier for a reaction by a certain amount and thereby speeds up the reaction 100-fold, and factor B, by acting on another aspect of the reaction, does likewise, then A and B acting in parallel will lower the barrier
Figure 7–21 Transcription activators can act at different steps. in addition to (A) promoting binding of additional transcription regulators and (B) assembling rnA polymerase at promoters, transcription activators are often needed (C) to release already assembled rnA polymerases from promoters or (D) to release rnA polymerase molecules that become stalled after transcribing about 50 nucleotides of rnA. the activities shown in figure 7–19 can affect each of these four steps.
by a double amount and speed up the reaction 10,000-fold. Even if A and B work simply by attracting the same protein, the affinity of that protein for the reaction site increases multiplicatively. Thus, transcription activators often exhibit transcriptional synergy, where several DNA-bound activator proteins working together produce a transcription rate that is much higher than the sum of their transcription rates working alone (Figure 7–22).
An important point is that a transcription activator protein must be bound to DNA to influence transcription of its target gene. And the rate of transcription of a gene ultimately depends upon the spectrum of regulatory proteins bound upstream and downstream of its transcription start site, along with the coactivator proteins they bring to DNA.
Although the “default” state of eukaryotic DNA packaged into nucleosomes is resistant to transcription, eukaryotes nonetheless use transcription regulators to
Figure 7–22 Transcriptional synergy.
this experiment compares the rate of transcription produced by three experimentally constructed regulatory regions in a eukaryotic cell and reveals transcriptional synergy, a greater than additive effect of multiple activators working together. for simplicity, coactivators have been omitted from the diagram.
Such transcriptional synergy is not only observed between different transcription activators from the same organism; it is also seen between activator proteins from different eukaryotic species when they are experimentally introduced into the same cell. this last observation reflects the high degree of conservation of the machinery responsible for eukaryotic transcription initiation.
recruitment of chromatin masking the activation surface for activator for repressor binding site recruitment of with the general transcription factors recruitment of TATA histone methyl transferase histone methylation proteins that bind to methylated histones