The CCAAT enhancer-binding protein (C/EBP)β and Nrf1 interact to regulate dentin sialophosphoprotein (DSPP) gene expression during odontoblast differentiation

Karthikeyan Narayanan, Amsaveni Ramachandran, Mathew Craig Peterson, Jianjun Hao, Anne Brit Kolstø, Alan D. Friedman, Anne George

Research output: Contribution to journalArticlepeer-review

Abstract

Terminal differentiation of odontoblasts, the principal cells in dentin formation, proceeds by synthesis of type I collagen and noncollagenous proteins. DSP and DPP are specific markers for terminally differentiated odontoblasts and are encoded by a single gene DSPP (dentin sialophosphoprotein). In an attempt to understand the molecular mechanisms required for tissue-specific expression of the DSPP gene, we have identified a novel interaction between two bZIP transcription factors, Nrf1 and the CCAAT enhancer-binding protein (C/ EBP)β. This interaction was confirmed by both immunoprecipitation and chromatin immunoprecipitation assays. In undifferentiated odontoblasts, Nrf1 and C/EBPβ repress DSPP promoter activity individually and synergistically by cooperatively interacting with each other. This mutual interaction is facilitated by the bZIP domains in both the proteins. The repression domain in both Nrf1 and C/EBPβ was determined, and deletion of this domain abolished transcriptional repression. In fully differentiated odontoblasts, the loss of interaction between Nrf1 and C/EBPβ results in an increased DSPP transcription. Further, this interaction was found to be dependent on phosphorylation at Ser599 of Nrf1. Thus, the physical interaction between Nrf1 and C/EBPβ provide a novel mechanism for the transcriptional regulation of DSPP in odontoblasts.

Original languageEnglish (US)
Pages (from-to)45423-45432
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number44
DOIs
StatePublished - Oct 29 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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