Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner

Karoline Briegel, Kim Chew Lim, Christian Plank, Hartmut Beug, James Douglas Engel, Martin Zenke

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

The GATA factors are a family of transcriptional regulatory proteins in eukaryotes that share extensive homology in their DNA-binding domains. One enigmatic aspect of GATA factor expression is that several GATA proteins, which ostensibly share the same DNA-binding site specificity, are coexpressed in erythroid cells. To elucidate the roles of individual GATA factors in erythropoiesis, conditional alleles of GATA-1, GATA-2, and GATA-3 were prepared by fusing each of the factors to the hormone-binding domain of the human estrogen receptor (ER). These GATA/ER chimeric factors were shown to be hormone-inducible trans-activating proteins in transient transfection assays. When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner. These phenotypic effects are specifically attributable to the action of ectopically expressed GATA-2/ER because erythroblasts expressing exogenous GATA-2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a hormone-responsive block in differentiation. Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells.

Original languageEnglish
Pages (from-to)1097-1109
Number of pages13
JournalGenes and Development
Volume7
Issue number6
StatePublished - Jun 1 1993
Externally publishedYes

Fingerprint

Estrogen Receptors
GATA Transcription Factors
Hormones
Erythroblasts
Erythroid Precursor Cells
GATA2 Transcription Factor
Erythroid Cells
Proteins
Erythropoiesis
DNA
Eukaryota
Transfection
Ectopic Gene Expression
Estrogens
Alleles
Binding Sites

Keywords

  • Conditional alleles
  • Erythroid differentiation
  • GATA transcription factors

ASJC Scopus subject areas

  • Developmental Biology
  • Genetics

Cite this

Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. / Briegel, Karoline; Lim, Kim Chew; Plank, Christian; Beug, Hartmut; Engel, James Douglas; Zenke, Martin.

In: Genes and Development, Vol. 7, No. 6, 01.06.1993, p. 1097-1109.

Research output: Contribution to journalArticle

Briegel, Karoline ; Lim, Kim Chew ; Plank, Christian ; Beug, Hartmut ; Engel, James Douglas ; Zenke, Martin. / Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner. In: Genes and Development. 1993 ; Vol. 7, No. 6. pp. 1097-1109.
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