Title | Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Pimanda JE, Ottersbach K, Knezevic K, Kinston S, Chan WYI, Wilson NK, Landry J-R, Wood AD, Kolb-Kokocinski A, Green AR, Tannahill D, Lacaud G, Kouskoff V, Göttgens B |
Journal | Proc Natl Acad Sci U S A |
Volume | 104 |
Issue | 45 |
Pagination | 17692-7 |
Date Published | 2007 Nov 6 |
ISSN | 0027-8424 |
Keywords | Animals, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Blood Vessels, Embryo, Mammalian, Enhancer Elements, Genetic, GATA2 Transcription Factor, Gene Expression Regulation, Hematopoiesis, Hematopoietic Stem Cells, Mice, Proto-Oncogene Protein c-fli-1, Proto-Oncogene Proteins |
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. |
DOI | 10.1073/pnas.0707045104 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 17962413 |
PubMed Central ID | PMC2077040 |
Grant List | G0300723 / / Medical Research Council / United Kingdom G0800784 / / Medical Research Council / United Kingdom / / Wellcome Trust / United Kingdom |