The STAT [signal transducer and activator of transcription (Stat)] proteins are transcription factors that mediate the effects of cytokines and growth factors on gene expression. Because the DNA binding motifs favored by various Stats are similar, it has not been clear how it is that particular Stats regulate specific sets of target genes. To search for possible cofactors, Goenka and Boothby used a yeast two-hybrid screen to identify mouse proteins that interacted with Stat6. They isolated a protein they call CoaSt6 (for collaborator of Stat6) that appears specifically to enhance gene expression by Stat6. The authors confirmed that endogenous Stat6 and CoaSt6 interacted in various cell lines. Expression of transfected CoaSt6 with reporter plasmids showed that Stat6-dependent transcription was enhanced, whereas Stat1-dependent transcription was not. Depletion of CoaSt6 from 293 cells with short hairpin RNAs inhibited interleukin-4-stimulated expression of the Stat6 target gene CD23 but had no effect on interferon-γ-induced transcription of the interferon regulatory factor (IRF-1) gene. Binding of cofactors in complexes at gene promoters is one way in which transcription factors are restricted to regulating specific target genes. The authors propose that CoaSt6 may be a factor that confers selective activation by Stat6 at target genes.
S. Goenka, M. Boothby, Selective potentiation of Stat-dependent gene expression by collaborator of Stat6 (CoaSt6), a transcriptional cofactor. Proc. Natl. Acad. Sci. U.S.A. 103, 4210-4215 (2006). [Abstract] [Full Text]