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

J. Biol. Chem., Vol. 282, Issue 31, 22344-22352, August 3, 2007

This Article Full Text Full Text (PDF) The The Supplemental Data All Versions of this Article: 282/31/22344    most recent M703475200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Meyer, M. B. Articles by Pike, J. W. Search for Related Content PubMed PubMed Citation Articles by Meyer, M. B. Articles by Pike, J. W. Social Bookmarking                      What's this?

Characterizing Early Events Associated with the Activation of Target Genes by 1,25-Dihydroxyvitamin D₃ in Mouse Kidney and Intestine in Vivo^*

From the Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53706

In this report, we explore the interaction of the vitamin D receptor (VDR) at regulatory sites within both the Cyp24a1 and the Trpv6 genes using chromatin immunoprecipitation techniques in a mouse model in vivo. We show that exogenous 1,25(OH)₂D₃ induces rapid VDR and RXR (retinoid X receptor) binding to the Cyp24a1 gene in both the kidney and the intestine and to the Trpv6 gene in the intestine. Separate studies of Trpv6 in vitro suggest that VDR binding occurs directly to VDR response elements located –2 and –4 kb upstream of the TSS. VDR binding is dose-dependent, demonstrating EC₅₀ values that are comparable with those for the induction of both Cyp24a1 and Trpv6 mRNA. Importantly, interaction of the VDR with these targets results in rapid changes in histone 4 acetylation as well as the recruitment of RNA polymerase II. The presence of both VDR and RNA polymerase II at these sites declines between 3–6 h, whereas the changes observed in acetylation decrease more slowly. Finally, we show that whereas mediator protein 1 is recruited to the Cyp24a1 promoter in the intestine, this coactivator is apparently not required for Trpv6 activation. These studies provide the first evidence for 1,25(OH)₂D₃-induced VDR interaction at key target genes in vivo, revealing the consequences of that interaction on the Cyp24a1 and Trpv6 genes.

Received for publication, April 25, 2007 , and in revised form, June 6, 2007.

^* This work was supported by National Institutes of Health Grants DK052459 and DK072281 (to J. W. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ To whom correspondence should be addressed: University of Wisconsin-Madison, 433 Babcock Dr., Madison, WI 53706. Fax: 608-263-7609; E-mail: pike{at}biochem.wisc.edu.

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

This article has been cited by other articles:

				A. Fukushima, Y. Aizaki, and K. Sakuma Short-Chain Fatty Acids Induce Intestinal Transient Receptor Potential Vanilloid Type 6 Expression in Rats and Caco-2 Cells J. Nutr., January 1, 2009; 139(1): 20 - 25. [Abstract] [Full Text] [PDF]

				Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1{alpha} PNAS, February 19, 2008; 105(7): 2598 - 2603.