Characteristics of three homologous 202 genes (Ifi202a, Ifi202b, and Ifi202c) from the murine interferon-activatable gene 200 cluster

The Ifi202 gene is part of the interferon-activatable murine gene 200 cluster on chromosome 1. Ifi202 encodes the p202 protein whose overexpression is growth inhibitory and which can bind and inhibit the activity of numerous transcription factors including c-Jun, c-Fos, NF-κB, E2F-1; E2F-4, MyoD, and myogenin. We report here the exon-intron structure of Ifi202 and the discovery of Ifi202b and Ifi202c, close homologs of Ifi202 (whose designation we now change to Ifi202a). Ifi202a, b, and c were colocalized to chromosome 1 bands H4-H5 by fluorescence in situ hybridization. Ifi202b encodes p202b, which is interferon-inducible and differs from p202a in only 7 of 445 amino acids. 202b mRNA is constitutively expressed in tissues in which 202a mRNA is expressed. Ifi202c is apparently an unexpressed pseudogene. In murine embryonic fibroblasts (MEFs) from 129 mice, the level of 202b mRNA is approximately half that of 202a mRNA. We knocked out the Ifi202a gene from 129 mice. The expression of 202b mRNA, but not 202a mRNA, persisted in the knockout mice and their MEFs at the same level as in wildtype mice. However, in MEFs from the knockout mice, the constitutive and interferon-induced levels of p202b were approximately as high as the constitutive and the interferon-induced levels of p202a-plus p202b, respectively, in MEFs from wildtype mice. These findings suggest dosage compensation at the posttranscriptional level. This might account for the apparent lack of phenotype of the knockout mice.