Open AccessTransgenic Analysis of the Stem Cell Leukemia +19 Stem Cell Enhancer in Adult and Embryonic Hematopoietic and Endothelial Cells
Author(s) -
Silberstein Lev,
Sánchez MaríaJosé,
Socolovsky Merav,
Liu Ying,
Hoffman Gary,
Kinston Sarah,
Piltz Sandie,
Bowen Mark,
Gambardella Laure,
Green Anthony R.,
Göttgens Berthold
Publication year - 2005
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2005-0090
Subject(s) - biology , enhancer , stem cell , embryonic stem cell , haematopoiesis , progenitor cell , endothelial stem cell , microbiology and biotechnology , enhancer rnas , transgene , hematopoietic stem cell , gene , gene expression , genetics , in vitro
Appropriate 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.