SWI SNF Enhanceosomes recruit chromatin remodelers nuc 1 GCN5 GCN5 CBP Enhanceosome The enhanceosome forms aSample Page binding site for GCN5, which binds and adds acetyl groups to nuc 1, 2. GCN5 complex The co-activator CBP binds, recruiting RNA pol II. SWI-SNF nudges aside nuc 2. RNA pol II CBP nuc 2 SWI SNF RNA pol II CBP The TATA-binding protein (TBP) binds to the newly exposed TATA box, allowing transcription to begin. TBP FIGURE 12-19 The B-interferon enhanceosome acts to move nucleosomes by recruiting the SWI-SNF complex. interacting correctly, they form a “landing pad,” a high- affinity binding site for the protein CBP, a co-activator protein that also recruits the transcriptional machinery. The large CBP protein also contains an intrinsic histone acetylase activity that modifies nucleosomes and facili- tates high levels of transcription. Although the B-interferon promoter is shown with- out nucleosomes in Figure 12-18, the enhanceosome is actually surrounded by two nucleosomes, called nuc 1 and nuc 2 in Figure 12-19. One of them, nuc 2, is strate- gically positioned over the TATA box and transcription start site. GCN5, another co-activator, binds and acety- lates the two nucleosomes. After acetylation, the acti- vating transcription factors recruit the co-activator CBP, the RNA pol II holoenzyme, and the SWI-SNF chroma- tin-remodeling complex. SWI-SNF is then positioned to nudge the nucleosome 37 bp off the TATA box, making the TATA box accessible to the TATA-binding protein and allowing transcription to be initiated. Cooperative interactions help to explain several per- plexing observations about enhancers. For example, they explain why mutating any one transcription factor or binding site dramatically reduces enhancer activity. They also explain why the distance between binding sites within the enhancer is such a critical feature. Fur- thermore, enhancers do not have to be close to the start site of transcription, as is the example shown in Figure 12-19. One characteristic of enhancers is that they can activate transcription when they are located at great distances from the promoter (>50 kb), either upstream or downstream from a gene or even in an intron. Enhancer-blocking insulators A regulatory element, such as an enhancer, that can act over tens of thousands of base pairs could interfere with the regulation of nearby genes. To prevent such promiscuous activation, regulatory elements called enhancer-blocking insulators have evolved. When positioned between an enhancer and a promoter, enhancer-blocking insulators prevent the enhancer from activating transcription at that promoter. Such insulators have no effect on the activation of other pro- moters that are not separated from their enhancers by the insulator (Figure 12-20). Several models have been proposed to explain how an insulator could block enhancer activity only when placed between an enhancer and a promoter. Many of the models, like the one shown in Figure 12-21, propose that the DNA is organized into loops containing active genes. According

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