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Molecular and Cellular Biology, February 2001, p. 1404-1415, Vol. 21, No. 4
Department of Biology, Boston University,
Boston, Massachusetts 02215
Received 31 October 2000/Accepted 21 November 2000
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
nucleosome-mediated 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.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.4.1404-1415.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Binding of TATA Binding Protein to a Naturally
Positioned Nucleosome Is Facilitated by Histone Acetylation
*
Corresponding author. Mailing address: Department of
Biology, Boston University, 5 Cummington St., Boston, MA 02215. Phone: (617) 353-8730. Fax: (617) 353-8734. E-mail: uhansen{at}bu.edu.
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