Transcriptional Regulation of the Stem Cell Leukemia Gene by PU.1 and Elf-1*
- Ernst-Otto Bockamp‡,
- Jeremy L. Fordham,
- Berthold Göttgens,
- Adelle M. Murrell,
- Maria-José Sanchez and
- Anthony R. Green§
- From the University of Cambridge, Department of Haematology, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom and ‡Johannes-Gutenberg University Mainz, Laboratory of Mouse Genetics, Institute of Toxikology, Obere Zahlbacher Strasse 67, 55131 Mainz, Germany
Abstract
The SCL gene, also known astal-1, encodes a basic helix-loop-helix transcription factor that is pivotal for the normal development of all hematopoietic lineages. SCL is expressed in committed erythroid, mast, and megakaryocytic cells as well as in hematopoietic stem cells. Nothing is known about the regulation of SCL transcription in mast cells, and in other lineages GATA-1 is the only tissue-specific transcription factor recognized to regulate the SCL gene. We have therefore analyzed the molecular mechanisms underlyingSCL expression in mast cells. In this paper, we demonstrate that SCL promoter 1a was regulated by GATA-1 together with Sp1 and Sp3 in a manner similar to the situation in erythroid cells. However, SCL promoter 1b was strongly active in mast cells, in marked contrast to the situation in erythroid cells. Full activity of promoter 1b was dependent on ETS and Sp1/3 motifs. Transcription factors PU.1, Elf-1, Sp1, and Sp3 were all present in mast cell extracts, bound to promoter 1b and transactivated promoter 1b reporter constructs. These data provide the first evidence that theSCL gene is a direct target for PU.1, Elf-1, and Sp3.
Footnotes
-
↵* This work was supported by the Cancer Research Campaign, the Wellcome Trust, the Leukaemia Research Fund, and the Association for International Cancer Research.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵§ To whom correspondence should be addressed: University of Cambridge, Department of Haematology, MRC Centre, Hills Road, Cambridge CB2 2QH. Tel.: 44-01223-336835; Fax: 44-01223-336827; E-mail:arg1000{at}cam.ac.uk.
-
- Received February 11, 1998.
- Revision received July 20, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
