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Transgenic analysis of the stem cell leukemia +19 stem cell enhancer in adult and embryonic hematopoietic and endothelial cells

AuthorsSilberstein, Lev; Sánchez, María José ; Socolovsky, Merav; Liu, Ying; Hoffman, Gary; Kinston, Sarah; Piltz, Sandie; Bowen, Mark; Gambardella, Laure; Green, Anthony R.; Göttgens, Berthold
KeywordsHematopoietic stem cell
Transcription factor SCL/tal-1
Transcriptional regulation
Experimental models
Issue Date1-Oct-2005
PublisherAlphaMed Press
CitationStem Cells 23(9): 1378-1388 (2005)
AbstractAppropriate transcriptional regulation is critical for the biological functions of many key regulatory genes, including the stem cell leukemia (SCL) gene. As part of a systematic dissection of SCL transcriptional regulation, we have previously identified a 5,245-bp SCL +18/19 enhancer that targeted embryonic endothelium together with embryonic and adult hematopoietic progenitors and stem cells (HSCs). This enhancer is proving to be a powerful tool for manipulating hematopoietic progenitors and stem cells, but the design and interpretation of such transgenic studies require a detailed understanding of enhancer activity in vivo. In this study, 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 5,245-bp +18/19 fragment both during development and 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 programs. Moreover, activity in a proportion of thymocytes and other SCL-negative cell types suggests the existence of a silencer elsewhere in the SCL locus.
Description11 páginas, 5 figuras, 1 tabla.
Publisher version (URL)http://dx.doi.org/10.1634/stemcells.2005-0090
Appears in Collections:(CABD) Artículos
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