Functional role of Zic2 phosphorylation in transcriptional regulation

Zic2 is a transcriptional activator that plays a crucial role in mammalian forebrain development. It activates the transcription of target genes by DNA binding and recruitment of RNA helicase A (RHA). We recently reported that the Zic2–RHA interaction is decreased by phosphatase treatment in vitro. We have now identified the phosphorylation site (serine 200) in mouse Zic2. Zic2S200A was defective in RHA-binding, and its transcriptional activation ability was diminished. These data indicate that Zic2S200 is a target for phosphorylation by DNA-dependent protein kinase, regulating Zic2-mediated transcriptional activation.