Repression of virus-induced interferon A promoters by homeodomain transcription factor Ptx1

Interferon A (IFN-A) genes are differentially expressed after virus inducti on. The differential expression of individual IFN-A genes is modulated by s ubstitutions in the proximal positive virus responsive element A (VRE-A) of their promoters and by the presence or absence of a distal negative regula tory element (DNRE). The functional feature of the DNRE is to specifically act by repression of VRE-A activity. With the use of the yeast one-hybrid s ystem, we describe here the identification of a specific DNRE-binding prote in, the pituitary homeobox 1 (Ptx1 or Pitx1), Ptx1 is detectable in differe nt cell types that differentially express IFN-A genes, and the endogenous P tx1 protein binds specifically to the DNRE. Upon virus induction, Ptx1 nega tively regulates the transcription of DNRE-containing IFN-A promoters, and the C-terminal region, as well as the homeodomain of the Ptx1 protein, is r equired for this repression. After virus induction, the expression of the P tx1 antisense RNA leads to a significant increase of endogenous IFN-A gene transcription and is able to modify the pattern of differential expression of individual IFN-A genes. These studies suggest that Ptx1 contributes to t he differential transcriptional strength of the promoters of different IFN- A genes and that these genes may provide new targets for transcriptional re gulation by a homeodomain transcription factor.