Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors
Copyright policy )Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors
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.
- University of Cambridge United Kingdom
- Nottingham Trent University United Kingdom
- University of Oxford United Kingdom
Embryo, Nonmammalian, Macromolecular Substances, Proto-Oncogene Protein c-fli-1, Helix-Loop-Helix Motifs, Molecular Sequence Data, Gene Expression Regulation, Developmental, Mice, Transgenic, Embryo, Mammalian, Hematopoietic Stem Cells, DNA-Binding Proteins, GATA2 Transcription Factor, Mice, Enhancer Elements, Genetic, Genes, Reporter, Multiprotein Complexes, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Amino Acid Sequence, Protein Binding
Embryo, Nonmammalian, Macromolecular Substances, Proto-Oncogene Protein c-fli-1, Helix-Loop-Helix Motifs, Molecular Sequence Data, Gene Expression Regulation, Developmental, Mice, Transgenic, Embryo, Mammalian, Hematopoietic Stem Cells, DNA-Binding Proteins, GATA2 Transcription Factor, Mice, Enhancer Elements, Genetic, Genes, Reporter, Multiprotein Complexes, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, Amino Acid Sequence, Protein Binding
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