Establishing the transcriptional programme for blood: The SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors

Berthold Göttgens, Aristotelis Nastos, Sarah Kinston, Sandra Piltz, Eric C.M. Delabesse, Maureen Stanley, Maria Jose Sanchez, Aldo Ciau-Uitz, Roger Patient, Anthony R. Green

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Stem cells are a central feature of metazoan biology. Haematopoietic stem cells (HSCs) represent the best-characterized example of this phenomenon, but the molecular mechanisms responsible for their formation remain obscure. The stem cell leukaemia (SCL) gene encodes a basic helix-loop-helix (bHLH) transcription factor with an essential role in specifying HSCs. Here we have addressed the transcriptional hierarchy responsible for HSC formation by characterizing an SCL 3′ enhancer that targets expression to HSCs and endothelium and their bipotential precursors, the haemangioblast. We have identified three critical motifs, which are essential for enhancer function and bind GATA-2, Fli-1 and Elf-1 in vivo. Our results suggest that these transcription factors are key components of an enhanceosome responsible for activating SCL transcription and establishing the transcriptional programme required for HSC formation.

Original languageEnglish
Pages (from-to)3039-3050
Number of pages12
JournalEMBO Journal
Volume21
Issue number12
DOIs
Publication statusPublished - 17 Jun 2002
Externally publishedYes

Keywords

  • Enhanceosome
  • SCL
  • Stem cell
  • Transcription

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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