Identification of Dentin Matrix Protein 1 (DMP1) as a Target for Regulation by Transcription Factor Ets2

概要

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Ets2 is a member of the Ets family of transcription factors that is involved in embryonic organ development. DMP1 is one of the chief non-collagenous proteins found in bone and mineralizing dentin. The DMP1 gene contains Ets binding sites in its regulatory sequences. Ets2 and DMP1 are co-expressed in certain tissues during tooth and craniofacial development. We therefore explored whether Ets2 regulates DMP1 expression. In the first approach, we determined the influence of elevated levels of Ets2 expression on DMP1 expression using Ets2-transfected MC3T3-E1 osteoblastic cells. The Ets2 expression vector is under the control of a mouse metallothionine promoter (mMT-1), which allows the controlled overexpression of Ets2 in the presence of Zn^<2+>. DMP1 expression was elevated significantly in MC3T3-E1 cells induced to overexpress Ets2, indicating that the Ets2 transcription factor regulates DMP1 expression in these cells. In the second set of experiments, we examined DMP1 expression in E13.5 Ets2 overexpression transgenic mouse embryos, by in situ hybridization. DMP1 expression was observed in ectopic sites such as the Meckel's cartilage, where DMP1 is not expressed during normal development at any developmental stage, whereas Ets2 is expressed during this stage. The in vitro and in vivo data taken together, strongly suggest that DMP1 is a target for regulation by Ets2.