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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 publication

DOI

10.1093/emboj/cdf286

Type

Journal article

Journal

EMBO J

Publication Date

17/06/2002

Volume

21

Pages

3039 - 3050

Keywords

Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, DNA-Binding Proteins, Embryo, Mammalian, Embryo, Nonmammalian, Enhancer Elements, Genetic, GATA2 Transcription Factor, Gene Expression Regulation, Developmental, Genes, Reporter, Helix-Loop-Helix Motifs, Hematopoietic Stem Cells, Humans, Macromolecular Substances, Mice, Mice, Transgenic, Molecular Sequence Data, Multiprotein Complexes, Protein Binding, Proto-Oncogene Protein c-fli-1, Proto-Oncogene Proteins, Sequence Alignment, Trans-Activators, Transcription Factors, Transcription, Genetic, Xenopus Proteins, Xenopus laevis