Interleukin-4-induced STAT6 Recognizes and Activates a Target Site in the Promoter of the Interleukin-4 Receptor Gene

This study addresses the function of STAT6 in interleukin-4-stimulated gene expression. A specific STAT6 DNA-binding target site has been identified in the promoter of the interleukin-4 receptor gene, and STAT6 is shown to be involved in mediating activation of gene expression via this site. STAT6 can mediate transcription of a heterologous reporter gene construct containing the interleukin-4 receptor STAT6 binding site. In addition, evidence is provided that demonstrates a distinct effect of STAT6 DNA binding specificity on transcriptional regulation since transcription was not stimulated from a competent but different DNA binding site. To confirm the role of STAT6 in gene activation, STAT6 mutant proteins were generated and analyzed for their ability to function in interleukin-4-induced transcription. Although the interleukin-2 gamma chain receptor subunit has been demonstrated to be a component of the interleukin-4 receptor, it is not required for specific gene activation.