Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
AuthorsPimanda, John E
Chan, Wan Y I
Wilson, Nicola K
Wood, Andrew D
Green, Anthony R
AffiliationDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom. firstname.lastname@example.org
MetadataShow full item record
AbstractConservation 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.
CitationGata2, 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.
JournalProceedings of the National Academy of Sciences
- The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype.
- Authors: Chan WY, Follows GA, Lacaud G, Pimanda JE, Landry JR, Kinston S, Knezevic K, Piltz S, Donaldson IJ, Gambardella L, Sablitzky F, Green AR, Kouskoff V, Göttgens B
- Issue date: 2007 Mar 1
- VEGFA-dependent and -independent pathways synergise to drive Scl expression and initiate programming of the blood stem cell lineage in Xenopus.
- Authors: Ciau-Uitz A, Pinheiro P, Kirmizitas A, Zuo J, Patient R
- Issue date: 2013 Jun
- Transcriptional link between blood and bone: the stem cell leukemia gene and its +19 stem cell enhancer are active in bone cells.
- Authors: Pimanda JE, Silberstein L, Dominici M, Dekel B, Bowen M, Oldham S, Kallianpur A, Brandt SJ, Tannahill D, Göttgens B, Green AR
- Issue date: 2006 Apr
- The scl +18/19 stem cell enhancer is not required for hematopoiesis: identification of a 5' bifunctional hematopoietic-endothelial enhancer bound by Fli-1 and Elf-1.
- Authors: Göttgens B, Broccardo C, Sanchez MJ, Deveaux S, Murphy G, Göthert JR, Kotsopoulou E, Kinston S, Delaney L, Piltz S, Barton LM, Knezevic K, Erber WN, Begley CG, Frampton J, Green AR
- Issue date: 2004 Mar
- Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis.
- Authors: Pimkin M, Kossenkov AV, Mishra T, Morrissey CS, Wu W, Keller CA, Blobel GA, Lee D, Beer MA, Hardison RC, Weiss MJ
- Issue date: 2014 Dec