Genes homologous to mouse Zfx have been identified on the X and Y chromosomes of all placental mammals examined. The genes of this ZFX/ZFY family appear to encode proteins comprising an amino-terminal acidic domain, a putative nuclear localizing signal, and a carboxy-terminal domain of 13 zinc fingers. These proteins likely function as transcription activators. Although roles for these proteins in sex determination, Turner syndrome, and spermatogenesis have been proposed, the biological processes in which these proteins function are not known. No comprehensive studies of gene structure have been reported for any member of the ZFX/ZFY family. Here, we report that mouse Zfx spans 50 kb and contains at least 11 exons. Exons 1 through 4 contain 5′ untranslated sequences, exons 5 through 10 encode the acidic domain, exon 10 also encodes the putative nuclear localizing signal, and exon 11 encodes 13 zinc fingers and contains the 3′ untranslated sequences. The 5′ untranslated exons exhibit complex patterns of differential splicing. At the 5′ end of this widely expressed gene, a 1.5-kb CpG island encompasses multiple transcription initiation sites as well as the first and second exons. The 5′ portion of the CpG island displays promoter activity. This knowledge of the Zfx gene structure allowed us to reconstruct the splicing and retroposition events by which the Zfa gene on mouse chromosome 10 arose from a Zfx transcript.
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