Article
- The EMBO Journal (2002) 21, 3039 - 3050
- doi:10.1093/emboj/cdf286
Subject Categories:
Establishing the transcriptional programme for blood: the SCL stem cell enhancer is regulated by a multiprotein complex containing Ets and GATA factors
Berthold Göttgens1, Aristotelis Nastos2, Sarah Kinston1, Sandie Piltz1, Eric C.M. Delabesse1, Maureen Stanley1, Maria-Jose Sanchez1, Aldo Ciau-Uitz2, Roger Patient2 and Anthony R. Green1
- University of Cambridge Department of Haematology, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, UK
- Institute of Genetics, Nottingham University, Queen's Medical Centre, Nottingham NG7 2UH, UK
Correspondence to:
Berthold Göttgens, E-mail: bg200@cam.ac.uk
Received 13 March 2002; Accepted 18 April 2002; Revised 18 April 2002
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.
Keywords:
- enhanceosome,
- SCL,
- stem cell,
- transcription
