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

2.50
Hdl Handle:
http://hdl.handle.net/10541/71227
Title:
Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development
Authors:
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; Tannahill, David; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold
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.
Affiliation:
Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom. jpimanda@unsw.edu.au
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.
Journal:
Proceedings of the National Academy of Sciences
Issue Date:
6-Nov-2007
URI:
http://hdl.handle.net/10541/71227
DOI:
10.1073/pnas.0707045104
PubMed ID:
17962413
Type:
Article
Language:
en
ISSN:
0027-8424
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPimanda, John E-
dc.contributor.authorOttersbach, Katrin-
dc.contributor.authorKnezevic, Kathy-
dc.contributor.authorKinston, Sarah-
dc.contributor.authorChan, Wan Y I-
dc.contributor.authorWilson, Nicola K-
dc.contributor.authorLandry, Josette-Renee-
dc.contributor.authorWood, Andrew D-
dc.contributor.authorKolb-Kokocinski, Anja-
dc.contributor.authorGreen, Anthony R-
dc.contributor.authorTannahill, David-
dc.contributor.authorLacaud, Georges-
dc.contributor.authorKouskoff, Valerie-
dc.contributor.authorGöttgens, Berthold-
dc.date.accessioned2009-06-23T11:50:05Z-
dc.date.available2009-06-23T11:50:05Z-
dc.date.issued2007-11-06-
dc.identifier.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.en
dc.identifier.issn0027-8424-
dc.identifier.pmid17962413-
dc.identifier.doi10.1073/pnas.0707045104-
dc.identifier.urihttp://hdl.handle.net/10541/71227-
dc.description.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.en
dc.language.isoenen
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshAnimals-
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors-
dc.subject.meshBinding Sites-
dc.subject.meshBlood Vessels-
dc.subject.meshEmbryo, Mammalian-
dc.subject.meshEnhancer Elements, Genetic-
dc.subject.meshGATA2 Transcription Factor-
dc.subject.meshGene Expression Regulation-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshMice-
dc.subject.meshProto-Oncogene Protein c-fli-1-
dc.subject.meshProto-Oncogene Proteins-
dc.titleGata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic developmenten
dc.typeArticleen
dc.contributor.departmentDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom. jpimanda@unsw.edu.auen
dc.identifier.journalProceedings of the National Academy of Sciencesen

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