TY - JOUR
T1 - The SCL transcriptional network and BMP signaling pathway interact to regulate RUNX1 activity
AU - Pimanda, John E.
AU - Donaldson, Ian J.
AU - De Bruijn, Marella F T R
AU - Kinston, Sarah
AU - Knezevic, Kathy
AU - Huckle, Liz
AU - Piltz, Sandie
AU - Landry, Josette Renée
AU - Green, Anthony R.
AU - Tannahill, David
AU - Göttgens, Berthold
PY - 2007/1/16
Y1 - 2007/1/16
N2 - 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. © 2007 by The National Academy of Sciences of the USA.
AB - 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. © 2007 by The National Academy of Sciences of the USA.
KW - Aorta-gonad-mesonephros
KW - Bioinformatics
KW - Hematopoiesis
KW - Hematopoietic stem cell
KW - SMAD6
U2 - 10.1073/pnas.0607196104
DO - 10.1073/pnas.0607196104
M3 - Article
C2 - 17213321
SN - 0027-8424
VL - 104
SP - 840
EP - 845
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 3
ER -
