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Coexpression of the interleukin-13 and interleukin-4 genes correlates with
their physical linkage in the cytokine gene cluster on human chromosome
5q23-31
G Dolganov, S Bort, M Lovett, J Burr, L Schubert, D Short, M McGurn, C Gibson and DB Lewis
Genelabs Incorporated, Redwood City, CA USA.
Interleukin-13 (IL-13) and IL-4 are cytokines produced by T cells that are
encoded by the q23-31 region of human chromosome 5. To investigate the
regulation of IL-13 gene expression by T cells, we isolated and sequenced
the human IL-13 gene, analyzed its 5'-flanking region for potential
transcriptional activation elements, and examined its expression in
nontransformed T-lineage cell populations. The human IL- 13 gene was
located 12.5-kb upstream of the IL-4 gene and 2-kb downstream of a CpG
island. The IL-13 gene 5' flank region included a segment with sequence
homology to P elements of the IL-4 promoter involved in transcriptional
activation in T cells. Mutation of the IL- 13 P element site significantly
reduced IL-13 promoter activity in response to T-cell activation.
Oligonucleotides containing the IL-13 or IL-4 P element sites specifically
bound the transcriptional activator protein, nuclear factor-activated T
cells, preformed (NF-ATp), when incubated with nuclear protein extracts
from activated T cells. Similar to IL-4, IL-13 mRNA expression was highest
in T-cell populations enriched for cells that had previously been primed in
vivo or in vitro, indicating that priming increases the expression of the
IL-13 and IL-4 genes in a coordinate manner. Because the primed T cells
contain higher levels of nuclear NF-ATp, capable of binding to P elements
of the IL-4 and IL-13 promoters, than do freshly-isolated T cells, the
NF-AT- binding P elements are attractive candidates to mediate the
coordinate expression of these two cytokine genes.
Volume 87,
Issue 8,
pp. 3316-3326,
04/15/1996
Copyright © 1996 by The American Society of Hematology
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