Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1

Nature. 1991 Jan 17;349(6306):257-60. doi: 10.1038/349257a0.

Abstract

The zinc-finger transcription factor GATA-1 (previously known as GF-1, NF-E1 or Eryf 1 binds to GATA consensus elements in regulatory regions of the alpha- and beta-globin gene clusters and other erythroid cell-specific genes. Analysis of the effects of mutations in GATA-binding sites in cell culture and in binding assays in vitro, as well as transactivation studies with GATA-1 expression vectors in heterologous cells, have provided indirect evidence that this factor is involved in the activation of globin and other genes during erythroid cell maturation. GATA-1 is also expressed in megakaryocytes and mast cells, but not in other blood cell lineages or in non-haemopoietic cells. To investigate the role of this factor in haematopoiesis in vivo, we disrupted the X-linked GATA-1 gene by homologous recombination in a male (XY) murine embryonic stem cell line and tested the GATA-1-deficient cells for their ability to contribute to different tissues in chimaeric mice. The mutant embryonic stem cells contributed to all non-haemopoietic tissues tested and to a white blood cell fraction, but failed to give rise to mature red blood cells. This demonstrates that GATA-1 is required for the normal differentiation of erythroid cells, and that other GATA-binding proteins cannot compensate for its absence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chimera
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Erythroid Precursor Cells / cytology
  • Erythroid-Specific DNA-Binding Factors
  • Erythropoiesis / genetics*
  • GATA1 Transcription Factor
  • Mice
  • Mutagenesis, Site-Directed
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Zinc Fingers / physiology

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Transcription Factors