United States Military HIV Research Program, Walter Reed Army Institute of Research, 1600 East Gude Drive, Rockville, Maryland, 20850, USA.
The chemokine receptor CCR3 has a critical function in the pathogenesis of eosinophilic diseases and is an entry co-receptor for HIV-1. We describe here the genomic organization and general transcriptional control mechanism for the human gene CCR3. We identified six cDNA transcripts formed by alternative splicing of eight exons and seven introns. CCR3 contains a 37-bp core promoter domain (-3 to +34 relative to the transcription start point) lacking a TATA box but inclusive of an initiator sequence, a G at +24, and a downstream promoter element (DPE) at +28 to +33 common for Drosophila melanogaster but heretofore described for only two other human genes. Mutation of these elements significantly attenuates CCR3 transcription, as predicted by a model of RNA pol II engagement with DPE-containing Drosophila promoters. These results provide evidence for the functional conservation of a DPE-dependent, general transcription control mechanism between Drosophila and human genes.