Cooperation of the transcriptional coactivators CBP and p300 with Stat6

Interleukin-4 (IL-4) functions as a critical regulatory cytokine of the imm une response. A major effect of IL-4 is the induction of specific gene expr ession mediated by activation of a latent transcription factor, Stat6. To u nderstand the mechanism by which Stat6 induces gene transcription, the effe cts of two histone acetylase coactivators, CREB binding protein (CBP) and p 300, were evaluated. Both CBP and p300 were found to cooperate with Sta6 fo r induction of Stat6-dependent transcription. This cooperation does not app ear to be due to acetylation of Stat6, The adenoviral E1A oncoprotein, know n to bind CBP and p300, can inhibit the ability of CBP and p300 to function as coactivators of Stat6, The cooperative effect of CBP and p300 depends o n the presence of a carboxyl-terminal region of Stat6, Stat6 molecules lack ing this region behave as negative interfering molecules for Stat6-dependen t transcription. Point mutations within this region also affect transcripti on by Stat6 in response to IL-4, identifying a motif that appears to be req uired for transcription, possibly through functional cooperation with CBP/p 300.