NDLI: The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity

Content Provider	PubMed Central
Author	Pimanda, John E. Donaldson, Ian J. Bruijn, Marella F. T. R. De Sarah, Kinston Knezevic, Kathy Huckle, Liz Piltz, Sandie Landry, Josette-renée Green, Anthony R. Tannahill, David Berthold, Göttgens
Copyright Year	2007
Abstract	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. Smad6, Bmp4, and Runx1 transcripts are concentrated along the ventral aspect of the E10.5 dorsal aorta in the aorta–gonad–mesonephros region from which HSCs originate. Moreover, Smad6, an inhibitor of Bmp4 signaling, binds and inhibits Runx1 activity, whereas Smad1, a positive mediator of Bmp4 signaling, transactivates the Runx1 promoter. Taken together, our results integrate three key determinants of HSC development; the Scl transcriptional network, Runx1 activity, and the Bmp4/Smad signaling pathway.
Related Links	http://dx.doi.org/10.1073/pnas.0607196104
Ending Page	845
Page Count	6
Starting Page	840
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	3
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-01-16
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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