Novel role for EKLF in megakaryocyte lineage commitment
Open Access
- 1 December 2007
- journal article
- Published by American Society of Hematology in Blood
- Vol. 110 (12) , 3871-3880
- https://doi.org/10.1182/blood-2007-03-082065
Abstract
Megakaryocytes and erythroid cells are thought to derive from a common progenitor during hematopoietic differentiation. Although a number of transcriptional regulators are important for this process, they do not explain the bipotential result. We now show by gain- and loss-of-function studies that erythroid Krüppel-like factor (EKLF), a transcription factor whose role in erythroid gene regulation is well established, plays an unexpected directive role in the megakaryocyte lineage. EKLF inhibits the formation of megakaryocytes while at the same time stimulating erythroid differentiation. Quantitative examination of expression during hematopoiesis shows that, unlike genes whose presence is required for establishment of both lineages, EKLF is uniquely down-regulated in megakaryocytes after formation of the megakaryocyte-erythroid progenitor. Expression profiling and molecular analyses support these observations and suggest that megakaryocytic inhibition is achieved, at least in part, by EKLF repression of Fli-1 message levels.Keywords
This publication has 74 references indexed in Scilit:
- Altered regulation of β-like globin genes by a redesigned erythroid transcription factorExperimental Hematology, 2007
- Transgene Insertion in Proximity to the c-myb Gene Disrupts Erythroid-Megakaryocytic Lineage BifurcationMolecular and Cellular Biology, 2006
- Alterations in Expression and Chromatin Configuration of the Alpha Hemoglobin-Stabilizing Protein Gene in Erythroid Krüppel-Like Factor-Deficient MiceMolecular and Cellular Biology, 2006
- Towards an understanding of lineage specification in hematopoietic stem cells: A mathematical model for the interaction of transcription factors GATA-1 and PU.1Journal of Theoretical Biology, 2006
- Stage-Specific Repression by the EKLF Transcriptional ActivatorMolecular and Cellular Biology, 2004
- Role of Ras signaling in erythroid differentiation of mouse fetal liver cells: functional analysis by a flow cytometry–based novel culture systemBlood, 2003
- Protein-Protein Interaction between Fli-1 and GATA-1 Mediates Synergistic Expression of Megakaryocyte-Specific Genes through Cooperative DNA BindingMolecular and Cellular Biology, 2003
- Ets-1 Regulates fli-1 Expression in Endothelial CellsPublished by Elsevier ,2002
- Preparation of Monoclonal Antibodies to Murine Platelet Glycoprotein IIb/IIIa (αIIbβ3) and Other Proteins from Hamster–Mouse Interspecies HybridomasBiochemical and Biophysical Research Communications, 1999
- Lethal β-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLFNature, 1995