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

• Published in: The EMBO journal 2002-06, Vol.21 (12), p.3039-3050
• Main Authors: Göttgens, Berthold, Nastos, Aristotelis, Kinston, Sarah, Piltz, Sandie, Delabesse, Eric C.M., Stanley, Maureen, Sanchez, Maria-Jose, Ciau-Uitz, Aldo, Patient, Roger, Green, Anthony R.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Basic Helix-Loop-Helix Transcription Factors; Cancer; DNA-Binding Proteins; DNA-Binding Proteins - metabolism; EMBO07; EMBO09; Embryo, Mammalian; Embryo, Mammalian - physiology; Embryo, Nonmammalian; enhanceosome; Enhancer Elements, Genetic; Enhancer Elements, Genetic - genetics; GATA2 Transcription Factor; Gene Expression Regulation, Developmental; Genes, Reporter; Helix-Loop-Helix Motifs; Helix-Loop-Helix Motifs - genetics; Hematopoietic Stem Cells; Hematopoietic Stem Cells - physiology; Humans; Leukemia; Life Sciences; Macromolecular Substances; Mice; Mice, Transgenic; Molecular Sequence Data; Multiprotein Complexes; Protein Binding; Proto-Oncogene Protein c-fli-1; Proto-Oncogene Proteins; Proto-Oncogene Proteins - metabolism; SCL; Sequence Alignment; stem cell; Stem cells; T-Cell Acute Lymphocytic Leukemia Protein 1; Trans-Activators; Trans-Activators - metabolism; transcription; Transcription Factors; Transcription Factors - metabolism; Transcription, Genetic; Xenopus laevis; Xenopus laevis - physiology; Xenopus Proteins
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/cdf286

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.