Search tips
Search criteria 


Logo of narLink to Publisher's site
Nucleic Acids Res. 1990 June 11; 18(11): 3261–3270.
PMCID: PMC330932

Two inflammatory mediator cytokine genes are closely linked and variably amplified on chromosome 17q.


Mitogenic stimulation of resting T cells results in the de novo transcription of a large number of genes including those encoding regulatory molecules such as lymphokines. The genomic organization of two newly described induced lymphokine genes, 464.1 and 744.1, has been determined. 464.1 and 744.1 appear to be the human homologues of the recently cloned murine macrophage inflammatory proteins, MIP-1 alpha and MIP-1 beta, respectively. The 464.1 and 744.1 genes share 55% amino acid homology and demonstrate parallel regulation of induced expression in T cells. It was therefore of interest to observe that these genes are closely linked in the human genome, separated by 14 kb, and are organized in a head to head fashion. Each of the genes is present in an additional nonallelic copy (referred to as 464.2 and 744.2) as part of an apparent amplification unit in the genome of many individuals. The 464.2 gene is expressed and potentially encodes a protein highly related to 464.1, varying in 5 of 92 amino acids. As expected, 464.2 and 744.2 are also closely linked to each other as determined by population linkage disequilibrium studies. Individuals bearing a chromosome with a third amplification event, involving a 464-related gene but not a 744-related gene, are also infrequently observed. These genes are all located on chromosome 17 in bands q11-q21, the region implicated in von Recklinghausen neurofibromatosis (NF1) and in acute promyelocytic leukemia (AML-M3).

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Crabtree GR. Contingent genetic regulatory events in T lymphocyte activation. Science. 1989 Jan 20;243(4889):355–361. [PubMed]
  • Irving SG, June CH, Zipfel PF, Siebenlist U, Kelly K. Mitogen-induced genes are subject to multiple pathways of regulation in the initial stages of T-cell activation. Mol Cell Biol. 1989 Mar;9(3):1034–1040. [PMC free article] [PubMed]
  • Zipfel PF, Balke J, Irving SG, Kelly K, Siebenlist U. Mitogenic activation of human T cells induces two closely related genes which share structural similarities with a new family of secreted factors. J Immunol. 1989 Mar 1;142(5):1582–1590. [PubMed]
  • Wolpe SD, Cerami A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 1989 Dec;3(14):2565–2573. [PubMed]
  • Wolpe SD, Davatelis G, Sherry B, Beutler B, Hesse DG, Nguyen HT, Moldawer LL, Nathan CF, Lowry SF, Cerami A. Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties. J Exp Med. 1988 Feb 1;167(2):570–581. [PMC free article] [PubMed]
  • Davatelis G, Tekamp-Olson P, Wolpe SD, Hermsen K, Luedke C, Gallegos C, Coit D, Merryweather J, Cerami A. Cloning and characterization of a cDNA for murine macrophage inflammatory protein (MIP), a novel monokine with inflammatory and chemokinetic properties. J Exp Med. 1988 Jun 1;167(6):1939–1944. [PMC free article] [PubMed]
  • Sherry B, Tekamp-Olson P, Gallegos C, Bauer D, Davatelis G, Wolpe SD, Masiarz F, Coit D, Cerami A. Resolution of the two components of macrophage inflammatory protein 1, and cloning and characterization of one of those components, macrophage inflammatory protein 1 beta. J Exp Med. 1988 Dec 1;168(6):2251–2259. [PMC free article] [PubMed]
  • Davatelis G, Wolpe SD, Sherry B, Dayer JM, Chicheportiche R, Cerami A. Macrophage inflammatory protein-1: a prostaglandin-independent endogenous pyrogen. Science. 1989 Feb 24;243(4894 Pt 1):1066–1068. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Chakravarti A, Buetow KH, Antonarakis SE, Waber PG, Boehm CD, Kazazian HH. Nonuniform recombination within the human beta-globin gene cluster. Am J Hum Genet. 1984 Nov;36(6):1239–1258. [PubMed]
  • Leitersdorf E, Chakravarti A, Hobbs HH. Polymorphic DNA haplotypes at the LDL receptor locus. Am J Hum Genet. 1989 Mar;44(3):409–421. [PubMed]
  • Kimura M. Estimation of evolutionary distances between homologous nucleotide sequences. Proc Natl Acad Sci U S A. 1981 Jan;78(1):454–458. [PubMed]
  • McBride OW, Hieter PA, Hollis GF, Swan D, Otey MC, Leder P. Chromosomal location of human kappa and lambda immunoglobulin light chain constant region genes. J Exp Med. 1982 May 1;155(5):1480–1490. [PMC free article] [PubMed]
  • McBride OW, Battey J, Hollis GF, Swan DC, Siebenlist U, Leder P. Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14. Nucleic Acids Res. 1982 Dec 20;10(24):8155–8170. [PMC free article] [PubMed]
  • McBride OW, Swan DC, Tronick SR, Gol R, Klimanis D, Moore DE, Aaronson SA. Regional chromosomal localization of N-ras, K-ras-1, K-ras-2 and myb oncogenes in human cells. Nucleic Acids Res. 1983 Dec 10;11(23):8221–8236. [PMC free article] [PubMed]
  • Morton CC, Kirsch IR, Taub R, Orkin SH, Brown JA. Localization of the beta-globin gene by chromosomal in situ hybridization. Am J Hum Genet. 1984 May;36(3):576–585. [PubMed]
  • Rollins BJ, Stier P, Ernst T, Wong GG. The human homolog of the JE gene encodes a monocyte secretory protein. Mol Cell Biol. 1989 Nov;9(11):4687–4695. [PMC free article] [PubMed]
  • Burd PR, Freeman GJ, Wilson SD, Berman M, DeKruyff R, Billings PR, Dorf ME. Cloning and characterization of a novel T cell activation gene. J Immunol. 1987 Nov 1;139(9):3126–3131. [PubMed]
  • Wilson SD, Billings PR, D'Eustachio P, Fournier RE, Geissler E, Lalley PA, Burd PR, Housman DE, Taylor BA, Dorf ME. Clustering of cytokine genes on mouse chromosome 11. J Exp Med. 1990 Apr 1;171(4):1301–1314. [PMC free article] [PubMed]
  • Mount SM. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. [PMC free article] [PubMed]
  • Kioussis D, Vanin E, deLange T, Flavell RA, Grosveld FG. Beta-globin gene inactivation by DNA translocation in gamma beta-thalassaemia. Nature. 1983 Dec 15;306(5944):662–666. [PubMed]
  • Grosveld F, van Assendelft GB, Greaves DR, Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. [PubMed]
  • Yang YC, Kovacic S, Kriz R, Wolf S, Clark SC, Wellems TE, Nienhuis A, Epstein N. The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5. Blood. 1988 Apr;71(4):958–961. [PubMed]
  • Le Beau MM, Epstein ND, O'Brien SJ, Nienhuis AW, Yang YC, Clark SC, Rowley JD. The interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5913–5917. [PubMed]
  • Sutherland GR, Baker E, Callen DF, Hyland VJ, Wong G, Clark S, Jones SS, Eglinton LK, Shannon MF, Lopez AF, et al. Interleukin 4 is at 5q31 and interleukin 6 is at 7p15. Hum Genet. 1988 Aug;79(4):335–337. [PubMed]
  • Takahashi M, Yoshida MC, Satoh H, Hilgers J, Yaoita Y, Honjo T. Chromosomal mapping of the mouse IL-4 and human IL-5 genes. Genomics. 1989 Jan;4(1):47–52. [PubMed]
  • Griffin CA, Emanuel BS, LaRocco P, Schwartz E, Poncz M. Human platelet factor 4 gene is mapped to 4q12----q21. Cytogenet Cell Genet. 1987;45(2):67–69. [PubMed]
  • Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, Bordoni R, Francke U, Derynck R. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin. EMBO J. 1988 Jul;7(7):2025–2033. [PubMed]
  • Larson RA, Kondo K, Vardiman JW, Butler AE, Golomb HM, Rowley JD. Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am J Med. 1984 May;76(5):827–841. [PubMed]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press