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J. Biol. Chem., Vol. 281, Issue 28, 19064-19071, July 14, 2006

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Dentin Matrix Protein 1 Regulates Dentin Sialophosphoprotein Gene Transcription during Early Odontoblast Differentiation^*

From the Department of Oral Biology, University of Illinois, Chicago, Illinois 60612

Dentin mineralization requires transcriptional mechanisms to induce a cascade of gene expression for progressive development of the odontoblast phenotype. During cytodifferentiation of odontoblasts there is a constant change of actively transcribed genes. Thus, tissue-specific matrix genes that are silenced in early differentiation are expressed during the terminal differentiation process. Dentin sialophosphoprotein (DSPP) is an extracellular matrix, prototypical dentin, and a bone-specific gene, however, the molecular mechanisms by which it is temporally and spatially regulated are not clear. In this report, we demonstrate that dentin matrix protein 1 (DMP1), which is localized in the nucleus during early differentiation of odontoblasts, is able to bind specifically with the DSPP promoter and activate its transcription. We have identified the specific promoter sequence that binds specifically to the carboxyl end of DMP1. The DNA binding domain in DMP1 resides between amino acids 420 and 489. A chromatin immunoprecipitation assay confirmed the in vivo association of DMP1 with the DSPP promoter. Interactions between DMP1 and DSPP promoter thus provide the foundation to understand how DMP1 regulates the expression of the DSPP gene.

Received for publication, January 24, 2006 , and in revised form, April 28, 2006.

^* This work was supported by National Institutes of Health Grants DE13836 and DE11657. 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: Dept. of Oral Biology, University of Illinois, 801 S. Paulina, Chicago, IL 60612. Tel.: 312-492-8821; Fax: 312-996-6044; E-mail: anneg{at}uic.edu.

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