Ectopic expression of a conditional GATA-2/estrogen receptor chimera arrests erythroid differentiation in a hormone-dependent manner.
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.
Institute of Molecular Pathology (IMP), Vienna, Austria.
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Briegel
K C
KC
Lim
C
C
Plank
H
H
Beug
J D
JD
Engel
M
M
Zenke
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002642:Chick Embryo; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000166:cytology*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis; D004967:Estrogens / Q000378:metabolism*; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011784:Quail; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D004967:Estrogens; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors