ArticleProceedings of the National Academy of Sciences of the United States of America1992
An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 81 citations in OpenAlex.
- Early growth response protein-1 (Egr-1) is preferentially expressed in T helper type 2 (Th2) cells and is involved in acute transcription of the Th2 cytokine interleukin-4.The Journal of biological chemistry · 2010Article
- Octamer proteins inhibit IL-4 gene transcription in normal human CD4 T cells.Genes and immunity · 2001Article
- Characterization of a novel negative regulatory element in the human interleukin 4 promoter.Leukemia · 2000Article
- Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation.The EMBO journal · 1999Article
- Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.The Journal of clinical investigation · 1997Article
- Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx: molecular cloning and functional characterization.Molecular biology of the cell · 1997Article
- Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy.Journal of medical genetics · 1996Article
- Nuclear factor of activated T cells is associated with a mast cell interleukin 4 transcription complex.Molecular and cellular biology · 1996Article
- Inhibition of NF-AT-dependent transcription by NF-kappa B: implications for differential gene expression in T helper cell subsets.Proceedings of the National Academy of Sciences of the United States of America · 1995Article
- The bovine interleukin-4 gene: genomic organization, localization, and evolution.Mammalian genome : official journal of the International Mammalian Genome Society · 1995Article
- Characterization of nuclear protein binding to a site in the long terminal repeat of a murine leukemia virus: comparison with the NFAT complex.Journal of virology · 1995Article
- A common factor regulates both Th1- and Th2-specific cytokine gene expression.The EMBO journal · 1994Article
- Multiple closely-linked NFAT/octamer and HMG I(Y) binding sites are part of the interleukin-4 promoter.Nucleic acids research · 1993Article
- Molecular dissection of the mouse interleukin-4 promoter.Proceedings of the National Academy of Sciences of the United States of America · 1993Article
- Identification of cis-acting regulatory elements controlling interleukin-4 gene expression in T cells: roles for NF-Y and NF-ATc.Molecular and cellular biology · 1993Article
- Transcription of the interleukin 4 gene is regulated by multiple promoter elements.The Journal of experimental medicine · 1993Article
- Characterization of cytokine LD78 gene promoters: positive and negative transcriptional factors bind to a negative regulatory element common to LD78, interleukin-3, and granulocyte-macrophage colony-stimulating factor gene promoters.Molecular and cellular biology · 1993Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have identified a DNA segment that confers responsiveness to antigen stimulation signals on the human interleukin (IL) 4 gene in Jurkat cells. The human IL-4 gene, of 10 kilobases, is composed of four exons and three introns. A cis-acting element (P sequence) resides in the 5' upstream region; no additional DNA segments with enhancer activity were identified in the human IL-4 gene. For further mapping purposes, a fusion promoter was constructed with the granulocyte/macrophage colony-stimulating factor basic promoter containing 60 base pairs of sequence upstream from the cap site of the mouse granulocyte/macrophage colony-stimulating factor gene and various lengths of the 5' upstream sequence of the IL-4 gene. The P sequence was located between positions -79 and -69 relative to the transcription start site of the human IL-4 gene, and this location was confirmed by base-substitution mutations. The plasmids carrying multiple copies of the P sequence showed higher responsiveness to the stimulation. The binding protein(s) that recognize the P sequence of the IL-4 gene were identified by DNA-mobility-shift assays. The binding of NF(P) (a DNA binding protein that specifically recognizes the P sequence) to the P sequence was abolished when oligonucleotides carrying base substitutions were used, indicating that the NF(P) interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for IL-4 expression in vivo. The P sequence does not share homology with the 5' upstream sequence of the IL-2 gene, even though surrounding sequences of the IL-4 gene share high homology with the IL-2 gene. We conclude that a different set of proteins recognize IL-2 and IL-4 genes.
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