Tgif1 Represses Apolipoprotein Gene Expression in Liver

TG-interacting factor (Tgif1) represses gene expression by interaction with general corepressors, and can be recruited to target genes by transforming growth factor beta (TGF beta) activated Smads, or by the retinoid X receptor (RXR). Here we show that Tgif1 interacts with the LXR alpha nuclear receptor and can repress transcription from a synthetic reporter activated by LXR alpha. In cultured cells reducing endogenous Tgif1 levels resulted in increased expression of LXR alpha target genes. To test the in vivo role of Tgif1, we analyzed LXR alpha-dependent gene expression in mice lacking Tgif1. In the livers of Tgif1 null mice, we observed significant derepression of the apolipoprotein genes, Apoa4 and Apoc2, suggesting that Tgif1 is an important in vivo regulator of apolipoprotein gene expression. In contrast, we observed relatively minimal effects on expression of other LXR target genes. This work suggests that Tgif1 can regulate nuclear receptor complexes, in addition to those containing retinoic acid receptors, but also indicates that there is some specificity to which NR target genes are repressed by Tgif1. J. Cell. Biochem. 111: 380-390, 2010. (C) 2010 Wiley-Liss, Inc.