Transcription factor CP2 modulates the expression of BMP-4 gene during differentiation of mesenchymal stem cellsTranscription factor CP2 modulates the expression of BMP-4 gene during differentiation of mesenchymal stem cells

초록

BMP-4, a member of TGF-b family, is known as an important factor on the chondrocyte differentiation, limb and eye development. When we searched for putative factor binding sites in the promoter region of mouse BMP-4 to understand developmental and tissue-tropic high expression of BMP-4, CP2 consensus binding sequences were identified in several regions. In this study, we demonstrated that CP2 modulates the expression of BMP-4 gene during differentiation of mesenchymal stem cells (MSCs). CP2 binds to two regions of BMP-4 promoter, from -715 to -676 and from -147 to -118. During MSC differentiation, the expression profiles of CP2 isoforms were co-related with the expression pattern of BMP-4. The regulatory effect of CP2 isoforms on the BMP-4 promoter was analyzed by overexpression of each CP2 isoform in MSCs, both individually and in combination. Interestingly, CP2-b and CP2-c up- and down-regulate, respectively, the transcription activity of the BMP-4 promoter. These data indicates that BMP-4 gene expression is antagonistically regulated by CP2-b and CP2-c, and also suggests that CP2 play a critical role on the formation of mesodermal tissue by regulating the expression of BMP-4.