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Identification and Functional Characterization of Distinct Critically Important Bone Morphogenetic Protein-specific Response Elements in the Id1 Promoter
Open accessAbstract
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.
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Metadata
- Authors
- Korchynskyi, O., & ten Dijke, P.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 277
- Issue
- 7
- Pages
- 4883-4891
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2166920557
- Cited by
- 881
- References
- 1
- FWCI
- 10.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
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