Levels of GATA-1/GATA-2 transcription factors modulate expression of embryonic and fetal hemoglobins

Pranvera Ikonomi, Constance Tom Noguchi, Webb Miller, Helina Kassahun, Ross Cameron Hardison, Alan N. Schechter

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Abstract

GATA transcription factors bind the consensus sequence WGATAR, present in the flanking regions of most erythroid specific genes. GATA-1 and GATA-2, coexpressed in erythroid cells, are important for expression of erythroid genes. To elucidate the role of specific GATA transcription factors on globin gene expression, we examined the human α- and β-globin gene clusters for all GATA sites. Conserved GATA sites were found in each of the hypersensitive sites in both β-and α clusters and in proximal regulatory regions of the ζ-, ε- and γ-globin but not the α, δ or β-globin genes. We then tested the effect of increasing levels of GATA-1 and GATA-2 on the expression of endogenous globin genes in human erythroid cells. Increasing GATA-1 levels in K562 cells decreased the levels of ε-globin mRNA but had no effect on the levels of expression of γ, ζ or α-globin genes. Increasing GATA-2 levels increased ε-globin and γ-globin transcripts. Increasing levels of GATA-1 also caused a decrease in the expression of endogenous GATA-2, while increased levels of GATA-2 had no effect on GATA-1 mRNA. Our results indicate a differential role of GATA-1 and -2 transcription factors on globin transcripts and suggest a correlation between the conservation of GATA sites in the regulatory regions and the ability of endogenous globin genes to respond to GATA transcription factors. They also suggest that quantitative changes in the levels of GATA-1 or GATA-2 can result in alterations of globin target gene expression and may participate in the ontogenic control of the globin genes.

Original languageEnglish (US)
Pages (from-to)277-287
Number of pages11
JournalGene
Volume261
Issue number2
DOIs
StatePublished - Dec 31 2000

Fingerprint

GATA2 Transcription Factor
Fetal Hemoglobin
Globins
GATA Transcription Factors
Genes
Erythroid Cells
Nucleic Acid Regulatory Sequences
Gene Expression
Messenger RNA
K562 Cells

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Ikonomi, Pranvera ; Noguchi, Constance Tom ; Miller, Webb ; Kassahun, Helina ; Hardison, Ross Cameron ; Schechter, Alan N. / Levels of GATA-1/GATA-2 transcription factors modulate expression of embryonic and fetal hemoglobins. In: Gene. 2000 ; Vol. 261, No. 2. pp. 277-287.
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Levels of GATA-1/GATA-2 transcription factors modulate expression of embryonic and fetal hemoglobins. / Ikonomi, Pranvera; Noguchi, Constance Tom; Miller, Webb; Kassahun, Helina; Hardison, Ross Cameron; Schechter, Alan N.

In: Gene, Vol. 261, No. 2, 31.12.2000, p. 277-287.

Research output: Contribution to journalArticle

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T1 - Levels of GATA-1/GATA-2 transcription factors modulate expression of embryonic and fetal hemoglobins

AU - Ikonomi, Pranvera

AU - Noguchi, Constance Tom

AU - Miller, Webb

AU - Kassahun, Helina

AU - Hardison, Ross Cameron

AU - Schechter, Alan N.

PY - 2000/12/31

Y1 - 2000/12/31

N2 - GATA transcription factors bind the consensus sequence WGATAR, present in the flanking regions of most erythroid specific genes. GATA-1 and GATA-2, coexpressed in erythroid cells, are important for expression of erythroid genes. To elucidate the role of specific GATA transcription factors on globin gene expression, we examined the human α- and β-globin gene clusters for all GATA sites. Conserved GATA sites were found in each of the hypersensitive sites in both β-and α clusters and in proximal regulatory regions of the ζ-, ε- and γ-globin but not the α, δ or β-globin genes. We then tested the effect of increasing levels of GATA-1 and GATA-2 on the expression of endogenous globin genes in human erythroid cells. Increasing GATA-1 levels in K562 cells decreased the levels of ε-globin mRNA but had no effect on the levels of expression of γ, ζ or α-globin genes. Increasing GATA-2 levels increased ε-globin and γ-globin transcripts. Increasing levels of GATA-1 also caused a decrease in the expression of endogenous GATA-2, while increased levels of GATA-2 had no effect on GATA-1 mRNA. Our results indicate a differential role of GATA-1 and -2 transcription factors on globin transcripts and suggest a correlation between the conservation of GATA sites in the regulatory regions and the ability of endogenous globin genes to respond to GATA transcription factors. They also suggest that quantitative changes in the levels of GATA-1 or GATA-2 can result in alterations of globin target gene expression and may participate in the ontogenic control of the globin genes.

AB - GATA transcription factors bind the consensus sequence WGATAR, present in the flanking regions of most erythroid specific genes. GATA-1 and GATA-2, coexpressed in erythroid cells, are important for expression of erythroid genes. To elucidate the role of specific GATA transcription factors on globin gene expression, we examined the human α- and β-globin gene clusters for all GATA sites. Conserved GATA sites were found in each of the hypersensitive sites in both β-and α clusters and in proximal regulatory regions of the ζ-, ε- and γ-globin but not the α, δ or β-globin genes. We then tested the effect of increasing levels of GATA-1 and GATA-2 on the expression of endogenous globin genes in human erythroid cells. Increasing GATA-1 levels in K562 cells decreased the levels of ε-globin mRNA but had no effect on the levels of expression of γ, ζ or α-globin genes. Increasing GATA-2 levels increased ε-globin and γ-globin transcripts. Increasing levels of GATA-1 also caused a decrease in the expression of endogenous GATA-2, while increased levels of GATA-2 had no effect on GATA-1 mRNA. Our results indicate a differential role of GATA-1 and -2 transcription factors on globin transcripts and suggest a correlation between the conservation of GATA sites in the regulatory regions and the ability of endogenous globin genes to respond to GATA transcription factors. They also suggest that quantitative changes in the levels of GATA-1 or GATA-2 can result in alterations of globin target gene expression and may participate in the ontogenic control of the globin genes.

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