| First Author | Korchynskyi O | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 7 | Pages | 4883-91 |
| PubMed ID | 11729207 | Mgi Jnum | J:242478 |
| Mgi Id | MGI:5905276 | Doi | 10.1074/jbc.M111023200 |
| Citation | Korchynskyi O, et al. (2002) Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter. J Biol Chem 277(7):4883-91 |
| abstractText | Transforming growth factor-beta (TGF-beta) family members, which include bone morphogenetic proteins (BMPs) and TGF-betas, elicit their cellular effects by activating specific Smad proteins, which control the transcription of target genes. BMPs and TGF-betas have overlapping as well as specific effects on mesenchymal cell differentiation for which the mechanisms are incompletely understood. Here we report that Id1, a dominant negative inhibitor of basic helix-loop-helix proteins, is a direct target gene for BMP. BMP, but not TGF-beta, strongly activates the Id1 promoter in an Smad-dependent manner. We identified two BMP-responsive regions in the mouse Id1 promoter, which contain three distinct sequence elements; one region contains two Smad binding elements (SBEs), and the other region contains a GGCGCC palindromic sequence flanked by two CAGC and two CGCC motifs. Whereas SBEs and GGCGCC sequence are critically important, the CAGC and CGCC motifs are needed for efficient BMP-induced Id1 promoter activation. Smads are part of nuclear transcription factor complexes that specifically bind to SBEs and GGCGCC sequence in response to BMP but not TGF-beta. Multimerization of the all three distinct sequence motifs is needed to generate a highly sensitive and BMP/Smad-dependent specific enhancer. Our results provide important new insights into how the BMP/Smad pathway can specifically activate target genes. |
