Abstract

Stat6 signaling pathways have been correlated with functional responses induced by IL-4 and PDGF that may play a role in human malignancy. Utilizing fluorescencein situhybridization, we mapped the human Stat6 gene to chromosome 12q bands 13.3–14.1, a breakpoint region implicated in a wide variety of solid tumors. To understand the genesis of three human Stat6 variant cDNAs, including a naturally occurring dominant negative species, we further characterized the genomic structure and flanking regions of the human Stat6 gene. The human Stat6 gene encompassed over 19 kb and contained 23 exons. For promoter studies, we introduced flanking sequence 5′ of Stat6 exon 1 into a promoterless luciferase reporter vector and characterized basal promoter activity by deletion analysis. DNA sequence analysis revealed potential transcriptional regulation of the putative promoter through numerous consensus binding elements. Finally, we conclude that selective exon deletion and utilization of alternative donor/acceptor sites appear to explain best human Stat6 variant mRNAs.

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