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Two conserved regions within the tissue-type plasminogen activator gene promoter mediate regulation by brain-derived neurotrophic factor.
- Source :
-
FEBS Journal . May2007, Vol. 274 Issue 9, p2411-2423. 13p. 1 Black and White Photograph, 2 Diagrams, 6 Graphs. - Publication Year :
- 2007
-
Abstract
- Tissue-type plasminogen activator (t-PA) has recently been identified as a modulator of neuronal plasticity and can initiate conversion of the pro-form of brain-derived neurotrophic factor (BDNF) into its mature form. BDNF also increases t-PA gene expression implicating t-PA as a downstream effector of BDNF function. Here we demonstrate that BDNF-mediated induction of t-PA mRNA requires an increase in t-PA gene transcription. Reporter constructs harboring 9.5 kb of the human t-PA promoter conferred BDNF-responsiveness in transfected mouse primary cortical neurons. This regulation was recapitulated in HEK 293 cells coexpressing the TrkB neurotrophin receptor. t-PA promoter-deletion analysis revealed the presence of two BDNF-responsive domains, one located between −3.07 and −2.5 kb and the other within the proximal promoter. The upstream region was shown to confer BDNF responsiveness in a TrkB-dependent manner when attached to a heterologous promoter. We also identify homologous regions within the murine and bovine t-PA gene promoters and demonstrate that the equivalent upstream murine sequence functions as a BDNF-responsive enhancer when inserted 5′ of the human proximal t-PA promoter. Hence, BDNF-mediated induction of t-PA transcription relies on conserved modular promoter elements including a novel upstream BDNF-responsive domain and the proximal t-PA gene promoter. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1742464X
- Volume :
- 274
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- FEBS Journal
- Publication Type :
- Academic Journal
- Accession number :
- 24732390
- Full Text :
- https://doi.org/10.1111/j.1742-4658.2007.05777.x