Gata2, Fli1, and Scl Form a Recursively Wired Gene-regulatory Circuit During Early Hematopoietic Development

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 Oct 27

PMID 17962413

Citations 115

Authors

John E Pimanda

Katrin Ottersbach

Kathy Knezevic

Sarah Kinston

Wan Y I Chan

Nicola K Wilson

Josette-Renee Landry

Andrew D Wood

Anja Kolb-Kokocinski

Anthony R Green

David Tannahill

Georges Lacaud

Valerie Kouskoff

Berthold Gottgens

Affiliations

Soon will be listed here.

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.

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