The scl +18/19 Stem Cell Enhancer Is Not Required for Hematopoiesis: Identification of a 5′ Bifunctional Hematopoietic-Endothelial Enhancer Bound by Fli-1 and Elf-1

Berthold Göttgens, Cyril Broccardo, Maria Jose Sanchez, Sophie Deveaux, George Murphy, Joachim R. Göthert, Ekaterini Kotsopoulou, Sarah Kinston, Liz Delaney, Sandra Piltz, Linda M. Barton, Kathy Knezevic, Wendy N. Erber, C. Glenn Begley, Jonathan Frampton, Anthony R. Green

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70 Citations (Scopus)

Abstract

Analysis of cis-regulatory elements is central to understanding the genomic program for development. The scl/tal-1 transcription factor is essential for lineage commitment to blood cell formation and previous studies identified an scl enhancer (the +18/19 element) which was sufficient to target the vast majority of hematopoietic stem cells, together with hematopoietic progenitors and endothelium. Moreover, expression of scl under control of the +18/19 enhancer rescued blood progenitor formation in scl-/- embryos. However, here we demonstrate by using a knockout approach that, within the endogenous scl locus, the +18/19 enhancer is not necessary for the initiation of scl transcription or for the formation of hematopoietic cells. These results led to the identification of a bifunctional 5′ enhancer (-3.8 element), which targets expression to hematopoietic progenitors and endothelium, contains conserved critical Ets sites, and is bound by Ets family transcription factors, including Fli-1 and Elf-1. These data demonstrate that two geographically distinct but functionally related enhancers regulate scl transcription in hematopoietic progenitors and endothelial cells and suggest that enhancers with dual hematopoietic-endothelial activity may represent a general strategy for regulating blood and endothelial development.

Original languageEnglish
Pages (from-to)1870-1883
Number of pages14
JournalMolecular and Cellular Biology
Volume24
Issue number5
DOIs
Publication statusPublished - 1 Mar 2004

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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