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The TATA sequence of the human, estrogen-responsive pS2 promoter is complexed in vivo with a rotationally and translationally positioned nucleosome (NUC T). Using a chromatin immunoprecipitation assay, we demonstrate that TATA binding protein (TBP) does not detectably interact with this genomic binding site in MCF-7 cells in the absence of transcriptional stimuli. Estrogen stimulation of these cells results in hyperacetylation of both histones H3 and H4 within the pS2 chromatin encompassing NUC T and the TATA sequence. Concurrently, TBP becomes associated with the pS2 promoter region. The relationship between histone hyperacetylation and the binding of TBP was assayed in vitro using an in vivo-assembled nucleosomal array over the pS2 promoter. With chromatin in its basal state, the binding of TBP to the pS2 TATA sequence at the edge of NUC T was severely restricted, consistent with our in vivo data. Acetylation of the core histones facilitated the binding of TBP to this nucleosomal TATA sequence. Therefore, we demonstrate that one specific, functional consequence of induced histone acetylation at a native promoter is the alleviation of nucleosomemediated repression of the binding of TBP. Our data support a fundamental role for histone acetylation at genomic promoters in transcriptional activation by nuclear receptors and provide a general mechanism for rapid and reversible transcriptional activation from a chromatin template.Transcription by RNA polymerase II (RNA pol II) from most eukaryotic promoters requires the evolutionarily conserved interaction of TATA binding protein (TBP) with a TATA sequence (42) in a chromatin context. Transcriptional activity, at least in yeast, correlates strongly with the degree of TBP occupancy of TATA box elements (30, 32). However, TBP can be severely inhibited from binding DNA sites located within unaltered mononucleosomes (17, 24). Positioning of a nucleosome over the TATA region appears to be a common mechanism for repressing basal transcription. In yeast, the TATA sequences of the inactive PHO5 (2), ADH2 (54), GAL80 (34,35), and CHA1 (37) promoters are all contained within positioned nucleosomes that are disrupted during induction-dependent chromatin rearrangements. Similar mechanisms have been observed in other organisms. Both the repressed human immunodeficiency virus type 1 promoter in unstimulated human T cells (53) and the inactive beta phaseolin gene in vegetative tobacco tissues (31) contain nucleosomes that occlude their respective TATA sequences and are subsequently disrupted concomitant with transcriptional activation.Of the multiple modifications required for conversion of chromatin from an inactive to active state, one consistent feature of active chromatin is the highly acetylated state of the core histones in the nucleosomes (13, 22, 52). Core histone acetylation influences both the interaction of specific proteins with nucleosomal DNA and the activation of gene expression (reviewed in reference 57). A broad range of transcriptional regulatory proteins possess ...

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