Identification and Functional Characterization of Distinct Critically Important Bone Morphogenetic Protein-specific Response Elements in the Id1 Promoter*
By O. Korchynskyi, P. ten Dijke. Journal of Biological Chemistry, 2002
895 citations recorded by the source corpus.
Transforming growth factor-β (TGF-β) family members, which include bone morphogenetic proteins (BMPs) and TGF-βs, elicit their cellular effects by activating specific Smad proteins, which control the transcription of target genes. BMPs and TGF-βs 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-β, 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-β. 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.
Subfields: Molecular Biology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/84e44f4bebd85613b45dbe418dded7c8af5e264d
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
- C. Hill
- Randall T. Peterson
- Bernhard Schmierer
- Clifford J. Woolf
- R. Ji
- Andrea Augello
- C. De Bari
- Arne May
In Pathology and Forensic Medicine
Citations in the corpus
- Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. (2008, background): “3 μg Id1 promoter luciferase reporter construct (BRE-Luc”
- Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression (2006, background): “Results Hemojuvelin is a BMP coreceptor To test whether hemojuvelin mediates BMP signaling in liver cells, we transfected hepatoma-derived HepG2 cells with a BMP-responsive luciferase reporter (BRE-Luc”
- TGFβ–SMAD signal transduction: molecular specificity and functional flexibility (2007, background): “Such BMP-responsive elements are found, for example, in the mammalian ID1 promote”