The alterations of chromatin structure that occur during transcription initiation can persist for different lengths of time. In some cases, as soon as the transcription regulator dissociates from DNA, the chromatin modifications are rapidly reversed, restoring the gene to its pre-activated state. This rapid reversal is especially important for genes that the cell must quickly switch on and off in response to external signals. In other cases, the altered chromatin structure persists, even after the transcription regulator that directed its establishment has dissociated from DNA. In principle, this memory can extend into the next cell generation because, as discussed in Chapter 4, chromatin structure can be self-renewing (see Figure 4–44). The fact that different histone modifications persist for different times provides the cell with a mechanism that makes possible both longerand shorter-term memory of gene expression patterns.
A special type of chromatin modification occurs as RNA polymerase II transcribes through a gene. The histones just ahead of the polymerase can be acetylated by enzymes carried by the polymerase, removed by histone chaperones, and deposited behind the moving polymerase. These histones are then rapidly deacetylated and methylated, also by complexes that are carried by the polymerase, leaving behind nucleosomes that are especially resistant to transcription. This remarkable process seems to prevent spurious transcription reinitiation
Figure 7–19 Eukaryotic transcription activator proteins direct local alterations in chromatin structure. nucleosome remodeling, nucleosome removal, histone replacement, and certain types of histone modifications favor transcription initiation (see figure 4–39). these alterations increase the accessibility of DnA and facilitate the binding of rnA polymerase and the general transcription factors.
Figure 7–20 Successive histone modifications during transcription initiation. in this example, taken from the human interferon gene promoter, a transcription activator binds to DnA packaged into chromatin and attracts a histone acetyl transferase that acetylates lysine 9 of histone h3 and lysine 8 of histone h4. then a histone kinase, also attracted by the transcription activator, phosphorylates serine 10 of histone h3 but it can only do so after lysine 9 has been acetylated. this serine modification signals the histone acetyl transferase to acetylate position K14 of histone h3. next, the general transcription factor tfiiD and a chromatin remodeling complex bind to the chromatin to promote the subsequent steps of transcription initiation. tfiiD and the remodeling complex both recognize acetylated histone tails through a bromodomain, a protein domain specialized to read this particular mark on histones; a bromodomain is carried in a subunit of each protein complex.
the histone acetyl transferase, the histone kinase, and the chromatin remodeling complex are all coactivators. the order of events shown applies to a specific promoter; at other genes, the steps may occur in a different order or individual steps may be omitted altogether. (Adapted from t. Agalioti, G. Chen and D. thanos, Cell 111:381–392, 2002. with  permission from elsevier.) behind a moving polymerase, which, in essence, must clear a path through chromatin as it transcribes. Later in this chapter, when we discuss RNA interference, the potential dangers to the cell of such inappropriate transcription will become especially obvious. The modification of nucleosomes behind a moving RNA polymerase also plays an important role in RNA splicing (see p. 323).
In some cases, transcription initiation requires that a DNA-bound transcription activator releases RNA polymerase from the promoter so as to allow it to begin transcribing the gene. In other cases, the RNA polymerase halts after transcribing about 50 nucleotides of RNA, and further elongation requires a transcription activator bound behind it (Figure 7–21). These paused polymerases are common in humans, where a significant fraction of genes that are not being transcribed have a paused polymerase located just downstream from the promoter.