An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals - PubMed (original) (raw)
Comparative Study
An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals
E Abe et al. Proc Natl Acad Sci U S A. 1992.
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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References
- EMBO J. 1989 May;8(5):1411-7 - PubMed
- Annu Rev Immunol. 1989;7:145-73 - PubMed
- Nature. 1988 Jun 23;333(6175):776-8 - PubMed
- Mol Cell Biol. 1988 Dec;8(12):5581-7 - PubMed
- Nucleic Acids Res. 1987 Jan 12;15(1):333-44 - PubMed
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