Transcriptional link between blood and bone: the stem cell leukemia gene and its +19 stem cell enhancer are active in bone cells.
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.
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, United Kingdom.
John E
JE
Pimanda
Lev
L
Silberstein
Massimo
M
Dominici
Benjamin
B
Dekel
Mark
M
Bowen
Scott
S
Oldham
Asha
A
Kallianpur
Stephen J
SJ
Brandt
David
D
Tannahill
Berthold
B
Göttgens
Anthony R
AR
Green
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics*; D001769:Blood / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009687:Nuclear Proteins; D010012:Osteogenesis; D051789:Proto-Oncogene Protein c-fli-1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D012863:Skeleton; D013234:Stem Cells / Q000166:cytology; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D009687:Nuclear Proteins; D051789:Proto-Oncogene Protein c-fli-1; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C512897:ELF1 protein, human; C512896:Elf1 protein, mouse; C497426:Fli1 protein, mouse; C494712:Gata2 protein, mouse; C489366:Tal1 protein, mouse