HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, J. Articles by Kemper, B. Search for Related Content PubMed PubMed Citation Articles by Kim, J. Articles by Kemper, B. Social Bookmarking                      What's this?

Volume 272, Number 47, Issue of November 21, 1997 pp. 29423-29425
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
Phenobarbital Alters Protein Binding to the CYP2B1/2 Phenobarbital-responsive Unit in Native Chromatin

(Received for publication, September 19, 1997)

From the Department of Molecular and Integrative Physiology and the College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801

Phenobarbital is a classical inducer of the drug metabolizing cytochrome P450 genes, but the molecular mechanism of induction has not been elucidated. Functional analyses have identified a phenobarbital-responsive unit in the rat CYP2B1/2 and mouse Cyp2b10 genes about 2.3 kilobase pairs from the transcriptional start site, but little or no changes in protein binding to this region were observed in vitro. To examine the role of chromatin structure, protein binding to the phenobarbital-responsive unit assessed by in vitro DNase I footprinting was compared with that assessed by DNase I in vivo footprints in native chromatin. A region centered on a putative nuclear factor-1 site was the major protected region in in vitro footprints, and there were no detectable differences in binding between extracts from control and phenobarbital-treated animals. In contrast, phenobarbital treatment dramatically altered the protection pattern in native chromatin. In control samples a core region of about 25 base pairs (bp) centered on the nuclear factor-1 site was protected. However, after phenobarbital treatment, the protection of this core region was increased, and more dramatically the region of protection was extended 20 bp to either side so that a total of about 60 bp were protected. These results provide the first evidence that phenobarbital treatment alters the composition or architecture of proteins binding to the phenobarbital-responsive unit region and indicate that chromatin structure is important in this process. Because proteins are bound to the region in the untreated animal, the mechanism of induction involves the activation of proteins bound to the region and possibly recruitment of additional regulatory proteins rather than conversion of a closed chromatin structure to an open one that can bind regulatory factors.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. K. Kemper, H. Kim, J. Miao, S. Bhalla, and Y. Bae Role of an mSin3A-Swi/Snf Chromatin Remodeling Complex in the Feedback Repression of Bile Acid Biosynthesis by SHP Mol. Cell. Biol., September 1, 2004; 24(17): 7707 - 7719. [Abstract] [Full Text] [PDF]

				C. Handschin and U. A. Meyer Induction of Drug Metabolism: The Role of Nuclear Receptors Pharmacol. Rev., December 1, 2003; 55(4): 649 - 673. [Abstract] [Full Text] [PDF]

				S. Gerbal-Chaloin, M. Daujat, J.-M. Pascussi, L. Pichard-Garcia, M.-J. Vilarem, and P. Maurel Transcriptional Regulation of CYP2C9 Gene. ROLE OF GLUCOCORTICOID RECEPTOR AND CONSTITUTIVE ANDROSTANE RECEPTOR J. Biol. Chem., January 4, 2002; 277(1): 209 - 217. [Abstract] [Full Text]

				K. Yoshinari, T. Sueyoshi, R. Moore, and M. Negishi Nuclear Receptor CAR as a Regulatory Factor for the Sexually Dimorphic Induction of CYP2B1 Gene by Phenobarbital in Rat Livers Mol. Pharmacol., February 1, 2001; 59(2): 278 - 284. [Abstract] [Full Text]

				S. H. Lee, X.-l. Wang, and J. DeJong Functional interactions between an atypical NF-{kappa}B site from the rat CYP2B1 promoter and the transcriptional repressor RBP-J{kappa}/CBF1 Nucleic Acids Res., May 15, 2000; 28(10): 2091 - 2098. [Abstract] [Full Text] [PDF]

				J. Kim, I. Rivera-Rivera, and B. Kemper Tissue-specific chromatin structure of the phenobarbital- responsive unit and proximal promoter of CYP2B1/2 and modulation by phenobarbital Nucleic Acids Res., March 1, 2000; 28(5): 1126 - 1132. [Abstract] [Full Text] [PDF]

				T. Kawamoto, T. Sueyoshi, I. Zelko, R. Moore, K. Washburn, and M. Negishi Phenobarbital-Responsive Nuclear Translocation of the Receptor CAR in Induction of the CYP2B Gene Mol. Cell. Biol., September 1, 1999; 19(9): 6318 - 6322. [Abstract] [Full Text] [PDF]

				T. Sueyoshi, T. Kawamoto, I. Zelko, P. Honkakoski, and M. Negishi The Repressed Nuclear Receptor CAR Responds to Phenobarbital in Activating the Human CYP2B6 Gene J. Biol. Chem., March 5, 1999; 274(10): 6043 - 6046. [Abstract] [Full Text] [PDF]

				S. C. Dogra, B. P. Davidson, and B. K. May Analysis of a Phenobarbital-Responsive Enhancer Sequence Located in the 5' Flanking Region of the Chicken CYP2H1 Gene: Identification and Characterization of Functional Protein-Binding Sites Mol. Pharmacol., January 1, 1999; 55(1): 14 - 22. [Abstract] [Full Text]

				E. T. Morgan, M. B. Sewer, H. Iber, F. J. Gonzalez, Y.-H. Lee, R. H. Tukey, S. Okino, T. Vu, Y.-H. Chen, J. S. Sidhu, et al. Physiological and Pathophysiological Regulation of Cytochrome P450 Drug Metab. Dispos., December 1, 1998; 26(12): 1232 - 1240. [Abstract] [Full Text]

				J. Zhang and X. Ding Identification and Characterization of a Novel Tissue-specific Transcriptional Activating Element in the 5'-Flanking Region of the CYP2A3 Gene Predominantly Expressed in Rat Olfactory Mucosa J. Biol. Chem., September 4, 1998; 273(36): 23454 - 23462. [Abstract] [Full Text] [PDF]

				T. A. Kocarek, J. M. Kraniak, and A. B. Reddy Regulation of Rat Hepatic Cytochrome P450 Expression by Sterol Biosynthesis Inhibition: Inhibitors of Squalene Synthase Are Potent Inducers of CYP2B Expression in Primary Cultured Rat Hepatocytes and Rat Liver Mol. Pharmacol., September 1, 1998; 54(3): 474 - 484. [Abstract] [Full Text]

				C. Stoltz, M.-H. Vachon, E. Trottier, S. Dubois, Y. Paquet, and A. Anderson The CYP2B2 Phenobarbital Response Unit Contains an Accessory Factor Element and a Putative Glucocorticoid Response Element Essential for Conferring Maximal Phenobarbital Responsiveness J. Biol. Chem., April 3, 1998; 273(14): 8528 - 8536. [Abstract] [Full Text] [PDF]

				P. Honkakoski, R. Moore, K. A. Washburn, and M. Negishi Activation by Diverse Xenochemicals of the 51-Base Pair Phenobarbital-Responsive Enhancer Module in the CYP2B10 Gene Mol. Pharmacol., April 1, 1998; 53(4): 597 - 601. [Abstract] [Full Text]

				Y. Paquet, E. Trottier, M.-J. Beaudet, and A. Anderson Mutational Analysis of the CYP2B2 Phenobarbital Response Unit and Inhibitory Effect of the Constitutive Androstane Receptor on Phenobarbital Responsiveness J. Biol. Chem., December 1, 2000; 275(49): 38427 - 38436. [Abstract] [Full Text] [PDF]

				J. Kim, G. Min, and B. Kemper Chromatin Assembly Enhances Binding to the CYP2B1 Phenobarbital-responsive Unit (PBRU) of Nuclear Factor-1, Which Binds Simultaneously with Constitutive Androstane Receptor (CAR)/Retinoid X Receptor (RXR) and Enhances CAR/RXR-mediated Activation of the PBRU J. Biol. Chem., March 2, 2001; 276(10): 7559 - 7567. [Abstract] [Full Text] [PDF]