Document Detail

Of the GATA-binding proteins, only GATA-4 selectively regulates the human IL-5 gene promoter in IL-5 producing cells which express multiple GATA-binding proteins.
MedLine Citation:
PMID:  9209438     Owner:  NLM     Status:  MEDLINE    
Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region, within the human IL-5 gene promoter, that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of these family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the -70 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Cotransfection experiments revealed that both hGATA-4 and PMA/A23187 stimulation are necessary for the IL-5 promoter activation. The requirement of another regulatory element called CLE0, which lies downstream of the -70 GATA site, was also demonstrated. ATL-16T cells express mRNA of three GATA-binding proteins, hGATA-2, hGATA-3 and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/ A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms specific DNA-protein complex with the -70 GATA site. The electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity to the -70 GATA site among the three GATA-binding proteins. When the transactivation ability was compared among the three, GATA-4 showed the highest activity. These results demonstrate the selective role of GATA-4 in the transcriptional regulation of the IL-5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed.
T Yamagata; J Nishida; R Sakai; T Tanaka; Y Yazaki; H Hirai
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Leukemia     Volume:  11 Suppl 3     ISSN:  0887-6924     ISO Abbreviation:  Leukemia     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-08-07     Completed Date:  1997-08-07     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  501-2     Citation Subset:  IM    
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MeSH Terms
Base Sequence
Binding Sites
Calcimycin / pharmacology
Cell Line
DNA-Binding Proteins / biosynthesis,  metabolism*
GATA2 Transcription Factor
GATA3 Transcription Factor
GATA4 Transcription Factor
Interleukin-5 / biosynthesis*,  genetics
Promoter Regions, Genetic*
Recombinant Proteins / biosynthesis
Regulatory Sequences, Nucleic Acid
Repetitive Sequences, Nucleic Acid
T-Lymphocytes / immunology
Tetradecanoylphorbol Acetate / pharmacology
Trans-Activators / biosynthesis
Transcription Factors / biosynthesis,  metabolism*
Transcription, Genetic*
Zinc Fingers
Reg. No./Substance:
0/DNA-Binding Proteins; 0/GATA2 Transcription Factor; 0/GATA2 protein, human; 0/GATA3 Transcription Factor; 0/GATA3 protein, human; 0/GATA4 Transcription Factor; 0/Interleukin-5; 0/Recombinant Proteins; 0/Trans-Activators; 0/Transcription Factors; 16561-29-8/Tetradecanoylphorbol Acetate; 52665-69-7/Calcimycin

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