Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter.
We show here that the immediate upstream region (from position -12 to -270) of the murine interleukin 4 (Il-4) gene harbors a strong cell-type specific transcriptional enhancer. In T lymphoma cells, the activity of the Il-4 promoter/enhancer is stimulated by phorbol esters, Ca++ ionophores and agonists of protein kinase A and inhibited by low doses of the immunosuppressant cyclosporin A. The Il-4 promoter/enhancer is transcriptionally inactive in B lymphoma cells and HeLa cells. DNase I footprint protection experiments revealed six sites of the Il-4 promoter/enhancer to be bound by nuclear proteins from lymphoid and myeloid cells. Among them are four purine boxes which have been described to be important sequence motifs of the Il-2 promoter. They contain the motif GGAAA and are recognized by the inducible and cyclosporin A-sensitive transcription factor NFAT-1. Three of the Il-4 NFAT-1 sites are closely linked to weak binding sites of Octamer factors. Several purine boxes and an AT-rich protein-binding site of the Il-4 promoter are also recognized by the high mobility group protein HMG I(Y). Whereas the binding of NFAT-1 and Octamer factors enhance the activity of the Il-4 promoter, the binding of HMG I(Y) suppresses its activity and, therefore, appears to be involved in the suppression of Il-4 transcription in resting T lymphocytes.
Chuvpilo
S
S
Institute of Pathology, Biozentrum, Am Hubland, University of Würzburg, Germany.
Schomberg
C
C
Gerwig
R
R
Heinfling
A
A
Reeves
R
R
Grummt
F
F
Serfling
E
E
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D004247:DNA