IRF- 1 and IRF-4 Regulate Target Gene Expression via Interaction with DMP 1

Interferon regulatory factor-4 (IRF-4), a member of the IRF gene family, is a lymphoid-specific transcription factor. IRF-4 deficient mice showed severe immunodeficiencies. Both B- and T-cell activation were profoundly affected: serum immunoglobulin concentrations and antibody responses were decreased, and cytotoxic and antitumor responses were absent in IRF-4 knockout mice. Thus, IRF-4 is essential for the functions of mature B- and T-lymphocytes. To analyze IRF-4 function, we searched for IRF-4- interacting factors. A plasmid was constructed to express a LexA-IRF-4 fusion protein from the inducible GAL1 promoter in yeast cells. When this low copy plasmid (pGilda/IRF-4) was introduced into the yeast strain NOY397, cell growth was significantly inhibited. We supposed that this growth inhibition arose from interference with cellular factors essential for cell viability. We isolated several genes that could rescue the growth inhibition phenotype by screening a yeast genomic library. One of the clones, encoding the REB1 protein, interacted with IRF-4 in vitro. The yeast REB1 protein shares homology with the human transcription factor DMP1. IRF-4 was shown to interact in vitro with DMP1, via its DNA binding domain. IRF-1 also interacted with DMP1. These results suggest that IRF-1 and IRF-4 might regulate target gene expression, via interactions with DMP1