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First published online 30 April 2008
doi: 10.1242/dev.018200

Development 135, 2071-2082 (2008)
Published by The Company of Biologists 2008
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Activation of Eklf expression during hematopoiesis by Gata2 and Smad5 prior to erythroid commitment

Felix Lohmann and James J. Bieker*

Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, Box 1020, 1 Gustave Levy Place, New York, NY 10029, USA.

* Author for correspondence (e-mail: james.bieker{at}mssm.edu)

Accepted 3 April 2008

The hierarchical progression of stem and progenitor cells to their more-committed progeny is mediated through cell-to-cell signaling pathways and intracellular transcription factor activity. However, the mechanisms that govern the genetic networks underlying lineage fate decisions and differentiation programs remain poorly understood. Here we show how integration of Bmp4 signaling and Gata factor activity controls the progression of hematopoiesis, as exemplified by the regulation of Eklf during establishment of the erythroid lineage. Utilizing transgenic reporter assays in differentiating mouse embryonic stem cells as well as in the murine fetal liver, we demonstrate that Eklf expression is initiated prior to erythroid commitment during hematopoiesis. Applying phylogenetic footprinting and in vivo binding studies in combination with newly developed loss-of-function technology in embryoid bodies, we find that Gata2 and Smad5 cooperate to induce Eklf in a progenitor population, followed by a switch to Gata1-controlled regulation of Eklf transcription upon erythroid commitment. This stage- and lineage-dependent control of Eklf expression defines a novel role for Eklf as a regulator of lineage fate decisions during hematopoiesis.

Key words: Megakaryocytic-erythroid progenitor, Lineage fate decision, ES cell in vitro differentiation, Eklf (Klf1)


Related articles in Development:

Eklf role in early haematopoiesis revealed

Development 2008 135: e1202. [Full Text]  



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T. Sengupta, K. Chen, E. Milot, and J. J. Bieker
Acetylation of EKLF Is Essential for Epigenetic Modification and Transcriptional Activation of the {beta}-Globin Locus
Mol. Cell. Biol., October 15, 2008; 28(20): 6160 - 6170.
[Abstract] [Full Text] [PDF]


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