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PMID: 1650452 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

GATA-1 transactivates erythropoietin receptor gene, and erythropoietin receptor-mediated signals enhance GATA-1 gene expression.

Nucleic acids research ·Vol. 19 ·No. 14 ·1991-07-25 ·Pages 3843-8

Chiba T, Ikawa Y, Todokoro K

Abstract

Erythropoietin is a cytokine which specifically regulates the proliferation and differentiation of erythroid progenitor cells. The expression of erythropoietin receptor on the cell membrane of the progenitor cells is a critical event during the erythroid differentiation process. In order to clarify the tissue-specific and differentiation stage-specific expression of the erythropoietin receptor gene, its transcriptional regulation was examined by transient expression assay, gel mobility shift assay and DNase I footprinting. The results clearly showed that GATA-1 transactivates the gene expression through a single GATA motif located around -200 bp upstream from the ATG codon in a dose dependent manner. Furthermore, Northern blot analysis revealed that erythropoietin receptor-mediated signals strongly enhanced GATA-1 gene expression in accordance with the appearance of hemoglobin-positive cells. Taken together with other observations, these results suggested the following scheme of erythroid differentiation: 1)GATA-1 is expressed in the early stage of blood cell development; 2) GATA-1 transactivates the erythropoietin receptor gene; 3) erythropoietin binds its receptor and the receptor-mediated signals enhance GATA-1 gene expression in erythroid progenitor cells; and 4) GATA-1 finally transactivates hemoglobin synthesis-related genes and globin genes in relatively matured erythroid cells.

Related Genes
MeSH Terms
Animals Base Sequence Cloning, Molecular DNA DNA-Binding Proteins/genetics,metabolism Deoxyribonuclease I/metabolism Erythroid-Specific DNA-Binding Factors Erythropoietin/metabolism GATA1 Transcription Factor Gene Expression Regulation Hematopoiesis/genetics Leukemia, Erythroblastic, Acute Mice Molecular Sequence Data Promoter Regions, Genetic Receptors, Cell Surface/genetics,metabolism Receptors, Erythropoietin Restriction Mapping Signal Transduction Transcription Factors/genetics,metabolism Transcriptional Activation Tumor Cells, Cultured
Chemicals
DNA-Binding Proteins Erythroid-Specific DNA-Binding Factors GATA1 Transcription Factor Gata1 protein, mouse Receptors, Cell Surface Receptors, Erythropoietin Transcription Factors Erythropoietin DNA Deoxyribonuclease I
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Chiba T
Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Ikawa Y
Todokoro K
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29 references, click to expand
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
Published
1991-07-25
Pages
3843-8
Language
English
Region
England
NLM ID
0411011
PMCID
PMC328472
Subset
IM
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