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

Stem Cells. 2005 Oct;23(9):1378-88. doi: 10.1634/stemcells.2005-0090. Epub 2005 Jul 28.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Bone Marrow Cells / cytology
  • Cell Lineage
  • Endothelial Cells / cytology
  • Endothelial Cells / enzymology
  • Enhancer Elements, Genetic / genetics*
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Enzymologic / genetics
  • Hematopoietic Stem Cells / cytology*
  • Male
  • Mast Cells / cytology
  • Mast Cells / enzymology
  • Megakaryocytes / cytology
  • Megakaryocytes / enzymology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Proto-Oncogene Proteins / genetics*
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / blood
  • beta-Galactosidase / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse
  • beta-Galactosidase