Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation.
Dentin mineralization requires transcriptional mechanisms to induce a cascade of gene expression for progressive develop- ment of the odontoblast phenotype. During cytodifferentiation of odontoblasts there is a constant change of actively tran- scribed genes. Thus, tissue-specific matrix genes that are silenced in early differentiation are expressed during the termi- nal differentiation process. Dentin sialophosphoprotein (DSPP) is an extracellular matrix, prototypical dentin, and a bone-spe- cific 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 odonto- blasts, is able to bind specifically with the DSPP promoter and activate its transcription. We have identified the specific pro- moter 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.