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

TLDR

Dentin mineralization depends on transcriptional cascades that shift gene expression during odontoblast differentiation, yet the temporal regulation of key matrix genes such as DSPP remains poorly understood. The study investigates whether nuclear DMP1 directly binds the DSPP promoter to activate its transcription during early odontoblast differentiation. The authors mapped the DMP1 binding site to the DSPP promoter, identified residues 420–489 as the DNA‑binding domain, and confirmed in vivo association by ChIP, establishing DMP1 as a transcriptional activator of DSPP.

Abstract

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.