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Molecular and Cellular Biology, April 2006, p. 2615-2625, Vol. 26, No. 7
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.7.2615-2625.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcriptional Link between Blood and Bone: the Stem Cell Leukemia Gene and Its +19 Stem Cell Enhancer Are Active in Bone Cells

John E. Pimanda,1,{dagger} Lev Silberstein,1,{dagger} Massimo Dominici,2 Benjamin Dekel,3 Mark Bowen,1 Scott Oldham,4 Asha Kallianpur,5 Stephen J. Brandt,5 David Tannahill,4 Berthold Göttgens,1 and Anthony R. Green1*

Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom,1 Division of Hematology-Oncology, University of Modena, 41100 Modena, Italy,2 Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel,3 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom,4 Division of Hematology-Oncology, Vanderbilt University Medical Center, and VA Tennessee Valley Healthcare System, Nashville, Tennessee 372325

Received 10 September 2005/ Returned for modification 8 October 2005/ Accepted 30 December 2005

Blood and vascular cells are generated during early embryogenesis from a common precursor, the hemangioblast. The stem cell leukemia gene (SCL/tal 1) encodes a basic helix-loop-helix transcription factor that is essential for the normal development of blood progenitors and blood vessels. We have previously characterized a panel of SCL enhancers including the +19 element, which directs expression to hematopoietic stem cells and endothelium. Here we demonstrate that SCL is expressed in bone primordia during embryonic development and in adult osteoblasts. Despite consistent expression in cells of the osteogenic lineage, SCL protein is not required for bone specification of embryonic stem cells. In transgenic mice, the SCL +19 core enhancer directed reporter gene expression to vascular smooth muscle and bone in addition to blood and endothelium. A 644-bp fragment containing the SCL +19 core enhancer was active in both blood and bone cell lines and was bound in vivo by a common array of Ets and GATA transcription factors. Taken together with the recent observation that a common progenitor can give rise to blood and bone cells, our results suggest that the SCL +19 enhancer targets a mesodermal progenitor capable of generating hematopoietic, vascular, and osteoblastic progeny.

* Corresponding author. Mailing address: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom. Phone: 44 (0) 1223 336 820. Fax: 44 (0) 1223 762 670. E-mail: arg1000{at}cam.ac.uk.

{dagger} These authors contributed equally to this work.

Molecular and Cellular Biology, April 2006, p. 2615-2625, Vol. 26, No. 7
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.7.2615-2625.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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