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Submitted on May 13, 2005
Accepted on June 27, 2005
Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, P.O. Box 12233 (MD E4-06), Research Triangle Park, NC USA 27709
* To whom correspondence should be addressed. E-mail: archer1{at}niehs.nih.gov.
Nuclear receptors are a large family of ligand dependent transcription factors that regulate important physiological processes. To activate or repress genes assembled naturally as chromatin, nuclear receptors recruit two distinct enzymatic activities, namely histone modifying enzymes and ATP-dependent chromatin remodeling complexes, to alter local chromatin structure at target gene promoters. In this review, we examine the functional relationship between ATP dependent chromatin remodeling complexes and nuclear receptors in the context of transcriptional regulation. Using the steroid responsive mouse mammary tumor virus (MMTV) promoter as a model system, we discuss in detail the molecular mechanisms underlying the recruitment of these complexes and subsequent chromatin structure changes catalyzed by this group of enzymes. In addition, we extend the discussion to other nuclear receptor regulated promoters including the pS2 promoter. Finally, we summarize specific principles governing this critical relationship, identify unanswered questions and discuss the potential application of these principles in rational drug design.
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