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FIGURE 17-14 Cooperative binding of activators, I tere are shown four ways that the binding of one protein to a site on DNA can help the binding of another to a nearby site. In pari (a) ts shown cooperative binding through direct interaction between the two proteins, as we saw for K repressor in Chapter 16, and will see between many regulators in eukaryotes as well. In (b) a similar effect is achieved by both proteins interacting with a common third protein. Parts (c) and (d) show indirect effects in which binding of one protein to its site on DNA within nucfeosomes helps binding of a second protein. In (c) the first protein recruits a nudeosome remodeller whose action reveals a binding site for a second protein. In part (d) the binding of the first protein to its srte occurs because that site is on the DNA |ust where it exits the nudeosome. By binding there, it unwinds the DNA from the nudeosome a little, revealing the binding site for the second protein. Each of these mechanisms can explain how one legulator can help others bind, or. indeed, how an activator can heip the transcription machinery bind to a promoter.

Signal Integration: the HO Gene Is Controlled by Two Regulators; One Recruits Nucleosonie Modifiers and the Other Recruits Mediator

Tbe yeast S. cerevisiae divides by budding. Thai is, instead of dividing to produce two identical daughter cells, the so-called mother cell buds to produce a daughter cell. We will focus here on the expression of a gene called HO. fWe need not concern ourselves with the function of this gene, which is described in Chaper 11.) The HO gene is exprossed only in mother cells and only at a certain point in the cell cycle. These two conditions are communicated to the gene through two activators: SW15 and SBF. SW15 binds to multiple sites some distance from the gene, the nearest being more than 1 kb from the promoter (Figure 17-15). SBF also binds multiple sites, but these are located closer to the promoter Why does expression of the gone depend on both activators?

SBF [which is active only at the correct stage of the cell cycle) cannot bind its sites unaided; their disposition within chromatin prohibits it. SWI5 (which acts only in the mother cell) can bind to its sites unaided but cannot, from that distance, activate the HO gene (remember that in yeast, activators do not work over long distances). SVVI5 can, however. Terrnit nucleosonie modifiers (a histnne acetyl transferase followed by Ihe remodelling enzyme SWl/SNF). These act on nucleosomes over the SBF sites. Thus, if both activators are present and active, the action of SWI5 enables SBF to bind, and that activalor, in turn, recruits the transcriptional machinery (by directly binding Mediator) arid activates expression of the gene.

Signal Integration: Cooperative Binding of Activators at the Human (i-Interferon Gene

The human ^-interferon gene is activated in ceils upon viral infection, Infection triggers three activators; NFkB, IKF, and Jun/ATF. These proteins bind cooperatively to sites adjacent to one another Within an enhancer located abuut 1 kb upstream of the promoter. The structure formed by these regulators bound to the enhancer is called an enhanceosome (Figure 17-16).

The binding of the activators is cooperative for two reasons. Firstv the activators interact with each other. Second, an additional protein,

FIGURE 17-15 Control of the HO gene.

SWI5 can bind its sites within chromatin unaided, but SBF cannot. Remade Iters and historic acetyiases recruited by SWIS alter nucleosomes over the SBF sites, allowing that activator to bind near the promoter and activate the gene. In the figure, (or simplicity, the nucleosomes ate not drawn. (Source: Adapted (mm Ptashne M> and Cann A 2002 Genes & Signals, p. 95, Fig 2-18. © Cold Spring Harbor Laboratory Press.)

chromatin remodeting complex j!> hrstone acetylase

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