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Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development.


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.

SUBMITTER: Pimanda JE 

PROVIDER: S-EPMC2077040 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development.

Pimanda John E JE   Ottersbach Katrin K   Knezevic Kathy K   Kinston Sarah S   Chan Wan Y I WY   Wilson Nicola K NK   Landry Josette-Renée JR   Wood Andrew D AD   Kolb-Kokocinski Anja A   Green Anthony R AR   Tannahill David D   Lacaud Georges G   Kouskoff Valerie V   Göttgens Berthold B  

Proceedings of the National Academy of Sciences of the United States of America 20071025 45


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 sh  ...[more]

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