The Human CC Chemokine Receptor 5 (CCR5) Gene

Abstract

and 3 are not interrupted by an intron. Exon 4 and portions of exon 3 are shared by all isoforms. Exon 4 contains the open reading frame, 11 nucleotides of the 5ⴕ-UTR and the complete 3ⴕ-UTR. 3) The transcripts ap- pear to be initiated from two distinct promoters: an upstream promoter (PU), upstream of exon 1, and a downstream promoter (PD), that includes the “intronic” region between exons 1 and 3. 4) PU and PD lacked the canonical TATA or CAAT motifs, and are AT-rich. 5) PD demonstrated strong constitutive promoter activity, whereas PU was a weak promoter in all three leukocyte cell environments tested (THP-1, Jurkat, and K562). 6) We provide evidence for polymorphisms in the noncod- ing sequences, including the regulatory regions and 5ⴕ- UTRs. The structure ofCCR5 was strikingly reminiscent of the overall structure of other chemokine/chemoat- tractant receptors, underscoring an important evolu- tionarily conserved function for a prototypical gene structure. This is the first description of functional pro- moters for any CC chemokine receptor gene, and we speculate that the complex pattern of splicing events and dual promoter usage may function as a versatile mechanism to create diversity and flexibility in the reg- ulation of CCR5 expression.