Histone acetylation correlates well with transcriptional activity, and histone acetyltransferases (HATs) selectively regulate subsets of target genes by mechanisms that remain unclear. Here, we provide in vivo evidence that the yeast transcriptional activator Gcn4 recruits Gcn5 HAT complexes to selective promoters positioned in natural or ectopic locations, thereby creating local domains of histone H3 hyperacetylation and subsequent transcriptional activation. A significant portion of the Gcn4-targeted histone acetylation by Gcn5 is independent of transcriptional activity. These observations provide strong evidence for promoter-selective, targeted histone acetylation by Gcn5 that facilitates transcription in a causal fashion. In addition, Gcn5 also functions in an untargeted manner to acetylate H3 on a genome-wide scale.
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