Key Concepts of Section 9.5

• Eukaryotic transcription activators and repressors exert their effects largely by binding to multisubunit co-activators or co-repressors that influence the assembly of preinitiation complexes either by modulating chromatin structure or by interacting with Pol II and general transcription factors.

• The DNA in condensed regions of chromatin (heterochromatin) is relatively inaccessible to transcription factors and other proteins, so that gene expression in these regions is repressed.

• The interactions of several proteins with one another and with the hypoacetylated N-terminal tails of histones H3 and H4 are responsible for the chromatin-mediated repression of transcription that occurs in the telomeres and the silent mating-type loci in S. cerevisiae (see Figure 9-36).

• Some repression domains function by interacting with co-repressors that are histone deacetylase complexes. The subsequent deacetylation of histone N-terminal tails in nucleosomes near the repressor-binding site inhibits interaction between the promoter DNA and general transcription factors, thereby repressing transcription initiation (see Figure 9-37a).

• Activation domains function by binding multiprotein co-activator complexes such as histone acetylase complexes. The subsequent hyperacetylation of histone N-terminal tails in nucleosomes near the activator-binding site facilitates interactions between the promoter DNA and general transcription factors, thereby stimulating transcription initiation (see Figure 9-37b).

• SWI/SNF chromatin-remodeling factors constitute another type of co-activator. These multisubunit complexes can transiently dissociate DNA from histone cores in an ATP-dependent reaction and may also decondense regions of chromatin, thereby promoting the binding of DNA-binding proteins needed for transcription initiation.

• The Mediator complex, another type of co-activator, is a roughly 30-subunit complex that forms a molecular bridge between activation domains and RNA polymerase II by binding directly to the polymerase and activation domains. By binding to several different activators either simultaneously or in rapid succession, Mediator probably helps integrate the effects of multiple activators on a single promoter (see Figure 9-40).

• Activators bound to a distant enhancer can interact with transcription factors bound to a promoter because chromatin is flexible and the intervening chromatin can form a large loop.

• The highly cooperative assembly of preinitiation complexes in vivo generally requires several activators. A cell must produce the specific set of activators required for transcription of a particular gene in order to express that gene.