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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2346-2354
CHEMOKINES
Analysis of the CC chemokine receptor 3 gene reveals a complex 5'
exon organization, a functional role for untranslated exon 1, and a
broadly active promoter with eosinophil-selective elements
Nives Zimmermann,
Bruce L. Daugherty,
Jessica L. Kavanaugh,
Faisal Y. El-Awar,
Elizabeth A. Moulton, and
Marc E. Rothenberg
To understand the regulation of CC chemokine receptor 3 (CCR3)
expression, its gene structure and promoter have been characterized. The CCR3 gene contains 4 exons that give rise to multiple
messenger RNA (mRNA) species by alternative splicing. Exon 1 is present in all transcripts, whereas exon 2 or 3 is present at low frequency (< 10%). Exon 4 contains the open reading frame and 11 bp of the 5'
untranslated region. Northern analysis revealed 4 species of CCR3 mRNA.
Direct sequencing revealed that the first 1 kb of the promoter and exon
1 contained only one mutation in 19 individuals, indicating that the
CCR3 promoter and exon 1 are conserved between individuals. The first
1.6 kb of the 5' flanking region of exon 1 contained promoter elements
including a TATA box and motifs for myeloid transcription factors
and had strong promoter activity in eosinophilic, lymphoid, myeloid,
and respiratory epithelial cell lines. Deletion analysis revealed
differential regulation of the CCR3 promoter in eosinophilic and
epithelial cells suggesting the presence of lineage-specific elements.
Interestingly, exon 1 enhanced the activity of the promoter and this
effect was especially prominent in eosinophilic cells. Thus, the human
CCR3 gene has a complex 5' exon structure, a conserved
promoter with strong activity in multiple cell types, and a functional
5' untranslated exon.
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