Constitutive Expression of GATA-1 Interferes With the Cell-Cycle Regulation

GATA-1, mainly expressed during erythroid differentiation, has been shown to regulate the genes specifically expressed in the late stages of erythropoiesis and to protect erythroid cells from apoptosis, suggesting that it might interfere with the cell cycle. By expressing the retrovirally transduced...

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Bibliographic Details
Published in:Blood 1996-05, Vol.87 (9), p.3711-3721
Main Authors: Dubart, A., Romeo, P.H., Vainchenker, W., Dumenil, D.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Base Sequence
Biological and medical sciences
Cell Cycle - physiology
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
DNA, Complementary
DNA-Binding Proteins - physiology
Erythroid-Specific DNA-Binding Factors
Fundamental and applied biological sciences. Psychology
GATA1 Transcription Factor
Gene Expression Regulation
Genetic Vectors
Humans
Mice
Molecular and cellular biology
Molecular Sequence Data
Retroviridae
Transcription Factors - physiology
Transfection
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Summary:GATA-1, mainly expressed during erythroid differentiation, has been shown to regulate the genes specifically expressed in the late stages of erythropoiesis and to protect erythroid cells from apoptosis, suggesting that it might interfere with the cell cycle. By expressing the retrovirally transduced human GATA-1 cDNA in NIH3T3 fibroblasts, we have shown that GATA-1 alone was unable to transactivate its erythroid-specific target genes in these nonerythroid cells. However, GATA-1 expression had a dramatic effect on the proliferation of these fibroblasts. The cloning efficiency of the GATA-1-expressing fibroblasts was maintained but their S phase was greatly elongated and their G1 and G2/M phases were reduced, impairing substantially their proliferation. When cultured at low serum concentrations for 48 hours, GATA-1-expressing fibroblasts failed to accumulate in the G0/G1 phases but did not become serum independent. GATA-1-expressing fibroblasts expressed D1, A, and B1 cyclin mRNAs under conditions of serum starvation or at confluence, whereas these cyclin mRNAs were downregulated in the parental NIH3T3 cells cultured under the same conditions. Moreover, these effects of GATA-1 expression on proliferation were not limited to NIH3T3 cells, since different clones of hGATA-1 virus-infected FDCP-1 cells, a murine in-terleukin-3-dependent hematopoietic cell line, had a slower growth rate than control cells. Based on these data, we hypothesize that GATA-1 plays a role in the regulation of the cell cycle during terminal erythroid differentiation.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V87.9.3711.bloodjournal8793711