Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
Pimanda, John E Ottersbach, Katrin Knezevic, Kathy Kinston, Sarah Chan, Wan Y I Wilson, Nicola K Landry, Josette-Renee Wood, Andrew D Kolb-Kokocinski, Anja Green, Anthony R
Pimanda, John E
Ottersbach, Katrin
Knezevic, Kathy
Kinston, Sarah
Chan, Wan Y I
Wilson, Nicola K
Landry, Josette-Renee
Wood, Andrew D
Kolb-Kokocinski, Anja
Green, Anthony R
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Abstract
Conservation of the vertebrate body plan has been attributed to the evolutionary stability of gene-regulatory networks (GRNs). We describe a regulatory circuit made up of Gata2, Fli1, and Scl/Tal1 and their enhancers, Gata2-3, Fli1+12, and Scl+19, that operates during specification of hematopoiesis in the mouse embryo. We show that the Fli1+12 enhancer, like the Gata2-3 and Scl+19 enhancers, targets hematopoietic stem cells (HSCs) and relies on a combination of Ets, Gata, and E-Box motifs. We show that the Gata2-3 enhancer also uses a similar cluster of motifs and that Gata2, Fli1, and Scl are expressed in embryonic day-11.5 dorsal aorta where HSCs originate and in fetal liver where they multiply. The three HSC enhancers in these tissues and in ES cell-derived hemangioblast equivalents are bound by each of these transcription factors (TFs) and form a fully connected triad that constitutes a previously undescribed example of both this network motif in mammalian development and a GRN kernel operating during the specification of a mammalian stem cell.
Description
Date
2007-11-06
Publisher
Collections
Keywords
Haematopoiesis
Haematopoietic Stem Cells
Haematopoietic Stem Cells
Type
Article
Citation
Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development. 2007, 104 (45):17692-7 Proc. Natl. Acad. Sci. U.S.A.