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Originally published In Press as doi:10.1074/jbc.C100315200 on July 11, 2001

J. Biol. Chem., Vol. 276, Issue 35, 32423-32426, August 31, 2001
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ACCELERATED PUBLICATION
Steroid Hormone Receptor-mediated Histone Deacetylation and Transcription at the Mouse Mammary Tumor Virus Promoter*

Lynn A. SheldonDagger §, Matthias Becker, and Catharine L. Smith

From the Dagger  Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756 and the  Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892

Acetylation of lysines in histones H3 and H4 N-terminal tails is associated with transcriptional activation and deacetylation with repression. Our studies with the mouse mammary tumor virus (MMTV) promoter in chromatin show significant levels of acetylation at promoter proximal and distal regions prior to transactivation. Upon activation with glucocorticoids or progestins, promoter proximal histones become deacetylated within the region of inducible nuclease hypersensitivity. The deacetylation lags behind the initiation of transcription, indicating a role in post-activation regulation. Our results indicate a novel mechanism by which target promoters are regulated by steroid receptors and chromatin modification machinery.

* This work was supported by grants from the Hitchcock Foundation, Dartmouth-Hitchcock Medical Center, and the Wendy Will Case Cancer Fund, Inc., Chicago, IL, and by American Cancer Society Institutional Research Grant IRG-82-003-17 (to L. A. S.) and National Institutes of Health Grant DK03535 (to Allan Munck).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Dept. of Physiology, 750W Borwell, 1 Medical Center Dr., Dartmouth Medical School, Lebanon, NH 03756. Tel.: 603-650-2479; Fax: 603-650-6130; E-mail: Lynn.A.Sheldon@dartmouth.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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