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

被引：99

作者：

Pimanda, John E.

Donaldson, Ian J.

de Bruijn, Marella F. T. R.

Kinston, Sarah

Knezevic, Kathy

Huckle, Liz

Piltz, Sandie

Landry, Josette-Renee

Green, Anthony R.

Tannahill, David

Gottgens, Berthold ^{[1
]}

机构：

[1] Univ Cambridge, Inst Med Res, Cambridge CB2 2XY, England

[2] John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England

[3] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 03期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

hematopoiesis; SMAD6; hematopoietic stem cell; aorta-gonad-mesonephros; bioinformatics;

D O I：

10.1073/pnas.0607196104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 Sd + 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.

引用

页码：840 / 845

页数：6

共 36 条

[1] Bone morphogenetic proteins regulate the developmental program of human hematopoietic stem cells [J].