Genome-wide computational screen for bloon stem cell enhancers integrates RUNX1 and the BMP signaling pathway into the SCL transcriptional network
| Autor: | Kathy Knezevic, Berthold Göttgens, Sandie Piltz, Ian J. Donaldson, Anthony R. Green, David Tannahill, Josette-Renee Landry, Liz Huckle, Sarah Kinston, Marella F. Bruijn, John E. Pimanda |
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| Rok vydání: | 2007 |
| Předmět: |
animal structures
Immunology SMAD Biology Biochemistry Genome chemistry.chemical_compound hemic and lymphatic diseases medicine Enhancer BMP signaling pathway Transcription factor Molecular Biology Hematopoietic stem cell Cell Biology Hematology Cell biology medicine.anatomical_structure RUNX1 chemistry embryonic structures Cancer research Molecular Medicine Signal transduction Stem cell TAL1 |
| Zdroj: | BLOOD CELLS MOLECULES AND DISEASES. 38(2) |
| ISSN: | 1079-9796 |
| Popis: | Hematopoietic stem cell (HSC) development is regulated by several signaling pathways and a number of key transcription factors, which include Scl/Tal1, Runx1 and members of the Smad family. However, it remains unclear how these various determinants interact. Using a genome-wide computational screen based on the well-characterized Scl +19 HSC enhancer, we have identified a related Smad6 enhancer that also targets expression to blood and endothelial cells in transgenic mice. We show that at E10.5, Smad6 and Bmp4 transcripts are concentrated along the ventral pole of the dorsal aorta and resemble Runx1 expression in the aorta-gonad-mesonephros (AGM) region where HSCs originate. Moreover, Smad6 binds and inhibits Runx1 activity whereas Smad1, a mediator of Bmp4 signaling, transactivates the Runx1 promoter. Taken together, our results integrate three key determinants of HSC development; the Scl network, Runx1 activity and the Bmp4/Smad signaling pathway. |
| Databáze: | OpenAIRE |
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