IDENTIFICATION OF A STAT6 DOMAIN REQUIRED FOR IL-4-INDUCED ACTIVATIONOF TRANSCRIPTION

Tyrosine phosphorylation of STAT6 in response to IL-4 results in the f ormation of STAT6 homodimers that hind specific DNA elements. Although binding sites for STAT6 have been shown to be important for the funct ion of several IL-4-inducible promoters, the role of STAT6 in this act ivation has not been defined. To determine whether STAT6 is a transcri ptional activator, different portions of the carboxyl terminus of STAT 6 were fused to the yeast Gal4 protein DNA binding domain. Analysis of these chimeric Gal4-STAT6 proteins demonstrates that a 140-amino-acid proline-rich region of the carboxyl terminus of STAT6 contains a regi on that activates transcription, Truncation mutants of STAT6 that lack this domain cannot activate transcription and are capable of repressi ng transcription stimulated by a wild-type STAT6 protein. Strikingly, the ability of IL-4 to induce transcription from the Ig germline epsil on promoter is suppressed by overexpression of a carboxyl-terminal del etion mutant of STAT6, These studies demonstrate that the carboxyl ter minus of STAT6 contains an activating domain required for the inductio n of genes by IL-4.