The first intron of the human alpha2(I) collagen gene (COL1A2) contains a novel interferon-gamma responsive element.

Cell transfection assays have shown that several transcription factors can mediate interferon-gamma (INF-gamma) inhibition of the human alpha2(I) collagen gene (COL1A2) by binding distinct cis-acting elements in the proximal promoter. Recent transgenic work, on the other hand, has identified a strong repressor in the first intron of COL1A2 that includes a binding site for interferon regulatory factors (IRFs). Here we present evidence from cell transfection experiments indicating that this IRF-binding site (IF3) is a novel target of the pathways elicited by INF-gamma to blunt transcription from the COL1A2 promoter. First, we showed that INF-gamma stimulates the production of IRF-1 transcripts, as well as the formation of an IRF-1 containing complex at the FI3 element. Second, we demonstrated that IRF-1 over-expression inhibits COL1A2 promoter activity specifically through the action of FI3, in addition to decreasing the steady-state levels of the endogenous COL1A2 mRNA. Third, we documented that INF-gamma treatment of cultured fibroblasts increases binding of IRF-1 to FI3 in the endogenous COL1A2 gene. Together our findings further extend the list of transcription factors involved in INF-gamma inhibition of COL1A2 gene expression.