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First published online July 28, 2005
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2005-0090v1
23/9/1378    most recent
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Submitted on March 3, 2005
Accepted on May 12, 2005

Original Article

Transgenic Analysis of the SCL +19 Stem Cell Enhancer in Adult and Embryonic Haematopoietic and Endothelial Cells

Lev Silberstein 1, Maria-Jose Sanchez 2, Merav Socolovsky 3, Ying Liu 3, Gary Hoffman 1, Sarah Kinston 1, Sandie Piltz 1, Mark Bowen 1, Laure Gambardella 4, Anthony R Green 1, Berthold Göttgens 1*

1 Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK
2 Centro Andaluz de Biologia del Desarrollo, Universidad Pablo de Olavide, Seville, Spain
3 University of Massachusetts Medical School, Department of Pediatrics (Hematology/Oncology Division) and Department of Cancer Biology, LRB Room 403, 364 Plantation Street, Worcester MA 01605, USA
4 The Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge, CB2 4AT, UK

* To whom correspondence should be addressed. E-mail: bg200{at}cam.ac.uk.


  Abstract

Appropriate transcriptional regulation is critical for the biological functions of many key regulatory genes including the stem cell leukaemia (SCL) gene. As part of a systematic dissection of SCL transcriptional regulation, we have previously identified a 5245 bp SCL+18/19 enhancer, which targeted embryonic endothelium together with embryonic and adult haematopoietic progenitors and stem cells (HSCs). This enhancer is proving to be a powerful tool for manipulating haematopoietic progenitors and stem cells, but the design and interpretation of such transgenic studies requires a detailed understanding of enhancer activity in vivo. Here we demonstrate that the +18/19 enhancer is active in mast cells, megakaryocytes and adult endothelium. A 644 bp +19 core enhancer exhibited similar temporal and spatial activity to the 5245 bp +18/19 fragment, both during development and also in adult mice. Unlike the +18/19 enhancer, the +19 core enhancer was only active in adult mice when linked to the eukaryotic reporter gene human placental alkaline phosphatase. Activity of a single core enhancer in HSCs, endothelium, mast cells and megakaryocytes suggests possible overlaps in their respective transcriptional programmes. Moreover, activity in a proportion of thymocytes and other SCL-negative cell types suggests the existence of a silencer elsewhere in the SCL locus.




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