The CCAAT enhancer-binding protein (C/EBP)beta and Nrf1 interact to regulate dentin sialophosphoprotein (DSPP) gene expression during odontoblast differentiation.
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)beta. This interaction was confirmed by both immunoprecipitation and chromatin immunoprecipitation assays. In undifferentiated odontoblasts, Nrf1 and C/EBPbeta 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/EBPbeta was determined, and deletion of this domain abolished transcriptional repression. In fully differentiated odontoblasts, the loss of interaction between Nrf1 and C/EBPbeta results in an increased DSPP transcription. Further, this interaction was found to be dependent on phosphorylation at Ser(599) of Nrf1. Thus, the physical interaction between Nrf1 and C/EBPbeta provide a novel mechanism for the transcriptional regulation of DSPP in odontoblasts.
Department of Oral Biology (M/C 690), University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Karthikeyan
K
Narayanan
Amsaveni
A
Ramachandran
Mathew Craig
MC
Peterson
Jianjun
J
Hao
Anne-Brit
AB
Kolstø
Alan D
AD
Friedman
Anne
A
George
D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000502:physiology*; D002460:Cell Line; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation; D016259:Genes, myc; D016350:Leucine Zippers; D051379:Mice; D051265:NF-E2-Related Factor 1; D009804:Odontoblasts / Q000378:metabolism*; D010006:Osteoblasts; D010750:Phosphoproteins; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D051381:Rats; D012694:Serine / Q000378:metabolism; D012795:Sialoglycoproteins; D014074:Tooth Calcification; D014157:Transcription Factors / Q000502:physiology*; D000099311:Dentin Sialophosphoprotein
D022782:CCAAT-Enhancer-Binding Protein-beta; D016326:Extracellular Matrix Proteins; D051265:NF-E2-Related Factor 1; D010750:Phosphoproteins; D011498:Protein Precursors; D012694:Serine; D012795:Sialoglycoproteins; D014157:Transcription Factors; D000099311:Dentin Sialophosphoprotein; C088357:NFE2L1 protein, human