An 11-base-pair DNA Sequence Motif Apparently Unique to the Human Interleukin 4 Gene Confers Responsiveness to T-cell Activation Signals

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Apr 1

PMID 1532661

Citations 15

Authors

E Abe

R de Waal Malefyt

I Matsuda

K Arai

N Arai

Affiliations

Soon will be listed here.

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.

Citing Articles

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.

Lohoff M, Giaisi M, Kohler R, Casper B, Krammer P, Li-Weber M J Biol Chem. 2009; 285(3):1643-52.

PMID: 19915002 PMC: 2804322. DOI: 10.1074/jbc.M109.011585.

Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation.

Li B, Tournier C, Davis R, Flavell R EMBO J. 1999; 18(2):420-32.

PMID: 9889198 PMC: 1171136. DOI: 10.1093/emboj/18.2.420.

Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

Batiuk T, Kung L, Halloran P J Clin Invest. 1997; 100(7):1894-901.

PMID: 9312192 PMC: 508377. DOI: 10.1172/JCI119719.

Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx: molecular cloning and functional characterization.

Liu J, Amasaki Y, Ikeuchi T, Imai S, Takano T, Arai N Mol Biol Cell. 1997; 8(1):157-70.

PMID: 9017603 PMC: 276067. DOI: 10.1091/mbc.8.1.157.

Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy.

Walley A, Cookson W J Med Genet. 1996; 33(8):689-92.

PMID: 8863163 PMC: 1050705. DOI: 10.1136/jmg.33.8.689.

References

Heike T, Miyatake S, Yoshida M, Arai K, Arai N . Bovine papilloma virus encoded E2 protein activates lymphokine genes through DNA elements, distinct from the consensus motif, in the long control region of its own genome. EMBO J. 1989; 8(5):1411-7. PMC: 400968. DOI: 10.1002/j.1460-2075.1989.tb03522.x. View

Mosmann T, Coffman R . TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989; 7:145-73. DOI: 10.1146/annurev.iy.07.040189.001045. View

Leung K, Nabel G . HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor. Nature. 1988; 333(6175):776-8. DOI: 10.1038/333776a0. View

Miyatake S, Seiki M, Yoshida M, Arai K . T-cell activation signals and human T-cell leukemia virus type I-encoded p40x protein activate the mouse granulocyte-macrophage colony-stimulating factor gene through a common DNA element. Mol Cell Biol. 1988; 8(12):5581-7. PMC: 365666. DOI: 10.1128/mcb.8.12.5581-5587.1988. View

Otsuka T, Villaret D, Yokota T, Takebe Y, Lee F, Arai N . Structural analysis of the mouse chromosomal gene encoding interleukin 4 which expresses B cell, T cell and mast cell stimulating activities. Nucleic Acids Res. 1987; 15(1):333-44. PMC: 340413. DOI: 10.1093/nar/15.1.333. View

Taniguchi T . Regulation of cytokine gene expression. Annu Rev Immunol. 1988; 6:439-64. DOI: 10.1146/annurev.iy.06.040188.002255. View

Durand D, Shaw J, Bush M, Replogle R, Belagaje R, Crabtree G . Characterization of antigen receptor response elements within the interleukin-2 enhancer. Mol Cell Biol. 1988; 8(4):1715-24. PMC: 363332. DOI: 10.1128/mcb.8.4.1715-1724.1988. View

Yokota T, Arai N, de Vries J, Spits H, Banchereau J, Zlotnik A . Molecular biology of interleukin 4 and interleukin 5 genes and biology of their products that stimulate B cells, T cells and hemopoietic cells. Immunol Rev. 1988; 102:137-87. DOI: 10.1111/j.1600-065x.1988.tb00744.x. View

Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K, Hamaoka T . Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982; 155(3):914-23. PMC: 2186613. DOI: 10.1084/jem.155.3.914. View

10.

ARAI K, Lee F, Miyajima A, Miyatake S, Arai N, Yokota T . Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990; 59:783-836. DOI: 10.1146/annurev.bi.59.070190.004031. View

11.

Novak T, Rothenberg E . cAMP inhibits induction of interleukin 2 but not of interleukin 4 in T cells. Proc Natl Acad Sci U S A. 1990; 87(23):9353-7. PMC: 55163. DOI: 10.1073/pnas.87.23.9353. View

12.

Ullman K, NORTHROP J, Verweij C, Crabtree G . Transmission of signals from the T lymphocyte antigen receptor to the genes responsible for cell proliferation and immune function: the missing link. Annu Rev Immunol. 1990; 8:421-52. DOI: 10.1146/annurev.iy.08.040190.002225. View

13.

Lowenthal J, Ballard D, Bohnlein E, Greene W . Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes. Proc Natl Acad Sci U S A. 1989; 86(7):2331-5. PMC: 286906. DOI: 10.1073/pnas.86.7.2331. View

14.

CROSS S, Halden N, Lenardo M, Leonard W . Functionally distinct NF-kappa B binding sites in the immunoglobulin kappa and IL-2 receptor alpha chain genes. Science. 1989; 244(4903):466-9. DOI: 10.1126/science.2497520. View

15.

Arai N, Nomura D, Villaret D, DeWaal Malefijt R, Seiki M, Yoshida M . Complete nucleotide sequence of the chromosomal gene for human IL-4 and its expression. J Immunol. 1989; 142(1):274-82. View

16.

Le Beau M, Lemons R, Espinosa 3rd R, Larson R, Arai N, Rowley J . Interleukin-4 and interleukin-5 map to human chromosome 5 in a region encoding growth factors and receptors and are deleted in myeloid leukemias with a del(5q). Blood. 1989; 73(3):647-50. View

17.

Muramatsu M, Kaibuchi K, Arai K . A protein kinase C cDNA without the regulatory domain is active after transfection in vivo in the absence of phorbol ester. Mol Cell Biol. 1989; 9(2):831-6. PMC: 362663. DOI: 10.1128/mcb.9.2.831-836.1989. View

18.

Noma Y, Sideras P, Naito T, Azuma C, Severinson E, Tanabe T . Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature. 1986; 319(6055):640-6. DOI: 10.1038/319640a0. View

19.

Lee F, Yokota T, Otsuka T, Meyerson P, Villaret D, COFFMAN R . Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986; 83(7):2061-5. PMC: 323230. DOI: 10.1073/pnas.83.7.2061. View

20.

Shaw J, Utz P, Durand D, Toole J, Emmel E, Crabtree G . Identification of a putative regulator of early T cell activation genes. Science. 1988; 241(4862):202-5. DOI: 10.1126/science.3260404. View