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gene silencing histone deposition gene expression

In addition to direct effects on nucleosomal function, modification of histone tails also generates binding sites for proteins (Figure 7-39b). Specific protein domains called bromodomains and chromodomains mediate these interactions. Bromodomain-containing proteins interact with acetylated histone tails and chromodomain-containing proteins interact with methylated histone tails. Many of the proteins that contain bromodomains are themselves associated with histone tail-specific acetyl transferases (Table 7-7). Such complexes can facilitate the maintenance of acetylated chromatin by further modifying regions that are already acetylated (as we shall discuss below). The association of chromodomain-containing proteins with histone tail-specific methyl-

FIGURE 7-39 Effects of histone tail modifications, (a) The effect on the association with nudeosome-bound DNA. Unmodified and methylated histone tails are thought to associate more tightly with nticteoscma! DNA than acelytated histone tads, (b) Modification of histone tails creates binding sites for chromatin-modifying enzymes.

FIGURE 7-39 Effects of histone tail modifications, (a) The effect on the association with nudeosome-bound DNA. Unmodified and methylated histone tails are thought to associate more tightly with nticteoscma! DNA than acelytated histone tads, (b) Modification of histone tails creates binding sites for chromatin-modifying enzymes.

ating enzymes suggests a similar mechanism for the maintenance of methylated nuclensomes (Table 7-7).

Other bromodnmain- and chromodomain-containing proteins are not histone modifying proteins but instead are proteins involved in regulating transcription or the formation of heterochromatin. For example, a key component of the transcription machinery called TFIID also includes a bromodomain. This domain directs the transcription machinery to sites of nucleosome acetylation, which contributes to the increased transcriptional activity of the DNA associated with acetylated nucleosomes. Similarly, nucleosome-remodeling complexes frequently include subunits with bromotlomains (Table 7-7).

Specific Enzymes Are Responsible for Histone Modification

The histone modifications we have just described are dynamic and are mediated by specific enzymes. Flistone acetyl transferases catalyze the addition of acetyl groups to the lysines of the histone N-lermini, whereas histone deacetylases remove these modifications. Similarly, histone methyl transferases add methyl groups to histones (histone demethylases have yet to be identified). A number of different histone acetyl transferases have been identified and are distinguished by their abilities to target different histones or even different lysines in the same histone tail. Similarly, each histone methyl transferase targets

174 Cht'omosorrles, Chromatin, and the Nur.leCsome TABLE 7-7 Nucleosome Modifying Enzymes

Histone Acetyl-transferase Complexes

174 Cht'omosorrles, Chromatin, and the Nur.leCsome TABLE 7-7 Nucleosome Modifying Enzymes

Histone Acetyl-transferase Complexes

Type Number of subunits

Catalytic subunit

Bromodomain/Chromodomain

Target histones

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