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

Lev Silberstein, María José Sánchez, Merav Socolovsky, Ying Liu, Gary Hoffman, Sarah Kinston, Sandra Piltz, Mark Bowen, Laure Gambardella, Anthony R. Green, Berthold Göttgens

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

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 find 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.

Original languageEnglish
Pages (from-to)1378-1388
Number of pages11
JournalStem Cells
Volume23
Issue number9
DOIs
Publication statusPublished or Issued - 1 Oct 2005
Externally publishedYes

Keywords

  • Experimental models
  • Hematopoietic stem cell
  • Transcription factor SCL/tal-1
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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