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

Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17692-7. doi: 10.1073/pnas.0707045104. Epub 2007 Oct 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Binding Sites
  • Blood Vessels / embryology
  • Blood Vessels / physiology
  • Embryo, Mammalian / physiology
  • Enhancer Elements, Genetic
  • GATA2 Transcription Factor / chemistry
  • GATA2 Transcription Factor / genetics
  • GATA2 Transcription Factor / metabolism*
  • Gene Expression Regulation
  • Hematopoiesis / physiology*
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Proto-Oncogene Protein c-fli-1 / chemistry
  • Proto-Oncogene Protein c-fli-1 / genetics
  • Proto-Oncogene Protein c-fli-1 / metabolism*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • T-Cell Acute Lymphocytic Leukemia Protein 1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Fli1 protein, mouse
  • GATA2 Transcription Factor
  • Gata2 protein, mouse
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse