Fractalkine shares signal sequence with TARC: Gene structures and expression profiles of two chemokine genes

In the process of cloning the gene (Scyd1) encoding the mouse CX3C chemokin e fractalkine, we identified a novel cDNA that encodes a chimeric molecule termed fracTARC. This molecule is a variant form of the mouse CC chemokine, TARC (for thymus- and activation-regulated chemokine), bearing the fractal kine signal sequence instead of its own. Analysis of the genomic organizati on of the two genes revealed that Scyd1 and Scya17, encoding TARC, are tigh tly linked on chromosome 8 and that fracTARC is generated by alternative sp licing of the two genes. Among tissues in which Scyd1 mRNA is expressed, fr acTARC mRNA is selectively expressed in brain and kidney, indicating that f racTARC mRNA is generated by tissue-specific alternative splicing under the control of the Scyd1 promoter. On the other hand, Scya17 and the fracTARC gene are reciprocally expressed in thymus, brain, lung, and kidney and are never expressed in the same tissue. These expression profiles indicate that tissue specificity of Scya17 is precisely regulated by two independent mec hanisms, one by transcription from its own promoter and the other from the promoter of Scyd1 followed by tissue-specific alternative splicing. These d ata provide evidence for a novel mechanism that controls gene expression of two independent genes of the same family. Such a mechanism may also operat e in other genes that are tightly linked on the same chromosome.