Role of PKCδ in IFN-γ-inducible CIITA gene expression

Abstract

The class II transactivator (CIITA) is a key regulatory factor for MHC class II expression. Here, we demonstrate that PKCδ plays an important role in regulating IFN-γ-inducible CIITA gene expression in macrophages. Inhibition of PKCδ by either a PKCδ inhibitor or a dominant negative (DN) mutant form of PKCδ led to down-regulation of CIITA expression. The decrease in CIITA expression by PKCδ inhibition was in part due to the reduced recruitment of serine 727-phosphorylated Stat1 and histone acetyltransferases to the CIITA promoter. As a result, IFN-γ induced histone acetylation at the CIITA promoter is also compromised. However, inhibition of PKCδ did not affect IRF-1 expression or IRF-1 binding to the CIITA promoter. Therefore, we report, for the first time, that PKCδ is an essential signaling molecule to achieve the maximal expression of CIITA in response to IFN-γ in macrophages. In addition, although IRF-1 is a key transcription factor to activate the IFN-γ inducible CIITA promoter, the effect of PKCδ on CIITA expression is mediated primarily by serine phosphorylation of Stat 1.