ATP-dependent nucleosome remodeling and histone hyperacetylation synergistically facilitate transcription of chromatin

Drosophila nucleosome remodeling factor (NURF) is an ISWI-containing protei n complex that facilitates nucleosome mobility and transcriptional activati on in an ATP-dependent manner. Numerous studies have implicated histone ace tylation in transcriptional activation. We investigated the relative contri butions of these two chromatin modifications to transcription in vitro of a chromatinized adenovirus E4 minimal promoter that contains binding sites f or the GAL4-VP16 activator. We found that NURF could remodel chromatin and stimulate transcription irrespective of the acetylation status of histones, In contrast, hyperacetylation of histones in the absence of NURF was unabl e to stimulate transcription, suggesting that NURF-dependent chromatin remo deling is an obligatory step in E4 promoter activation. When chromatin temp lates were first hyperacetylated and then incubated with NURF, significantl y greater transcription stimulation was observed. The results suggest that changes in chromatin induced by acetylation of histones and the mobilizatio n of nucleosomes by NURF combine synergistically to facilitate transcriptio n. Experiments using single and multiple rounds of transcription indicate t hat these chromatin modifications stimulate transcription preinitiation as well as reinitiation.