FIGURE 9-37 Proposed mechanism of histone deacetylation and hyperacetylation in yeast transcriptional control. (a) Repressor-directed deacetylation of histone N-terminal tails. The DNA-binding domain (DBD) of the repressor Ume6 interacts with a specific upstream control element of the genes it regulates, called URS1. The Ume6 repression domain (RD) binds Sin3, a subunit of a multiprotein complex that includes Rpd3, a histone deacetylase. Deacetylation of histone N-terminal tails on nucleosomes in the region of the Ume6-binding site inhibits binding of general transcription factors at the TATA box, thereby repressing gene expression. (b) Activator-directed hyperacetylation of histone N-terminal tails. The DNA-binding domain of the activator Gcn4 interacts with specific upstream activating sequences (UAS) of the genes it regulates. The Gcn4 activation domain (AD) then interacts with a multiprotein histone acetylase complex that includes the Gcn5 catalytic subunit. Subsequent hyperacetylation of histone N-terminal tails on nucleosomes in the vicinity of the Gcn4-binding site facilitates access by the general transcription factors required for initiation. Repression and activation of many genes in higher eukaryotes occur by similar mechanisms.