The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype.
AuthorsChan, Wan Y I
Follows, George A
Pimanda, John E
Donaldson, Ian J
Green, Anthony R
AffiliationDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, United Kingdom.
MetadataShow full item record
AbstractTranscription factors are key regulators of hematopoietic stem cells (HSCs), yet the molecular mechanisms that control their expression are largely unknown. Previously, we demonstrated that expression of Scl/Tal1, a transcription factor required for the specification of HSCs, is controlled by Ets and GATA factors. Here we characterize the molecular mechanisms controlling expression of Lyl1, a paralog of Scl also required for HSC function. Two closely spaced promoters directed expression to hematopoietic progenitor, megakaryocytic, and endothelial cells in transgenic mice. Conserved binding sites required for promoter activity were bound in vivo by GATA-2 and the Ets factors Fli1, Elf1, Erg, and PU.1. However, despite coregulation of Scl and Lyl1 by the same Ets and GATA factors, Scl expression was initiated prior to Lyl1 in embryonic stem (ES) cell differentiation assays. Moreover, ectopic expression of Scl but not Lyl1 rescued hematopoietic differentiation in Scl-/- ES cells, thus providing a molecular explanation for the vastly different phenotypes of Scl-/- and Lyl1-/- mouse embryos. Furthermore, coregulation of Scl and Lyl1 later during development may explain the mild phenotype of Scl-/- adult HSCs.
CitationThe paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype. 2007, 109 (5):1908-16 Blood
- The scl +18/19 stem cell enhancer is not required for hematopoiesis: identification of a 5' bifunctional hematopoietic-endothelial enhancer bound by Fli-1 and Elf-1.
- Authors: Göttgens B, Broccardo C, Sanchez MJ, Deveaux S, Murphy G, Göthert JR, Kotsopoulou E, Kinston S, Delaney L, Piltz S, Barton LM, Knezevic K, Erber WN, Begley CG, Frampton J, Green AR
- Issue date: 2004 Mar
- Fli1, Elf1, and Ets1 regulate the proximal promoter of the LMO2 gene in endothelial cells.
- Authors: Landry JR, Kinston S, Knezevic K, Donaldson IJ, Green AR, Göttgens B
- Issue date: 2005 Oct 15
- Lineage-restricted regulation of the murine SCL/TAL-1 promoter.
- Authors: Bockamp EO, McLaughlin F, Murrell AM, Göttgens B, Robb L, Begley CG, Green AR
- Issue date: 1995 Aug 15
- The SCL complex regulates c-kit expression in hematopoietic cells through functional interaction with Sp1.
- Authors: Lécuyer E, Herblot S, Saint-Denis M, Martin R, Begley CG, Porcher C, Orkin SH, Hoang T
- Issue date: 2002 Oct 1
- Role of SCL/Tal-1, GATA, and ets transcription factor binding sites for the regulation of flk-1 expression during murine vascular development.
- Authors: Kappel A, Schlaeger TM, Flamme I, Orkin SH, Risau W, Breier G
- Issue date: 2000 Nov 1