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 chemokine 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 fractalkine signal sequence instead of its own. Analysis of the genomic organization of the two genes revealed that Scyd1 and Scya17, encoding TARC, are tightly linked on chromosome 8 and that fracTARC is generated by alternative splicing of the two genes. Among tissues in which Scyd1 mRNA is expressed, fracTARC mRNA is selectively expressed in brain and kidney, indicating that fracTARC 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 mechanisms, one by transcription from its own promoter and the other from the promoter of Scyd1 followed by tissue-specific alternative splicing. These data provide evidence for a novel mechanism that controls gene expression of two independent genes of the same family. Such a mechanism may also operate in other genes that are tightly linked on the same chromosome.
Hiroyama
T
T
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
Iwama
A
A
Nakamura
Y
Y
Nakauchi
H
H
D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism; D054414:Chemokine CCL17; D054428:Chemokine CX3CL1; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics*; D020523:Chemokines, CX3C / Q000096:biosynthesis* / Q000235:genetics*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D007438:Introns; D007668:Kidney / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014158:Transcription, Genetic
C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D054428:Chemokine CX3CL1; D019742:Chemokines, CC; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger