The scl+19 cell enhancer is not required for haematopoiesis: identification of a second bifunctional hematopoietic/endothelial enhancer regulated by Fil-1 and Elf-1

Research output: Contribution to journalArticle

Authors

  • B Gottgens
  • C Broccardo
  • M-J Sanchez
  • S Deveaux
  • J Gothert
  • E Kotsopouloul
  • S Kinston
  • E Delaney
  • S Piltz
  • LM Barton
  • K Knezevic
  • WN Erber
  • CG Begley
  • AR Green

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 set 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.

Details

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