Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter - PubMed (original) (raw)
. 2002 Feb 15;277(7):4883-91.
doi: 10.1074/jbc.M111023200. Epub 2001 Nov 29.
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- PMID: 11729207
- DOI: 10.1074/jbc.M111023200
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Identification and functional characterization of distinct critically important bone morphogenetic protein-specific response elements in the Id1 promoter
Olexander Korchynskyi et al. J Biol Chem. 2002.
Free article
Abstract
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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