Vigilin interacts with CTCF and is involved in the maintenance of imprinting of IGF2 through a novel RNA-mediated mechanism.

Accumulating evidence has revealed the imprinting of insulin-like growth factor-2 gene (IGF2) is maintained by binding of CCCTC binding factor (CTCF) to the unmethylated imprinting control region (ICR) between IGF2 and H19 genes. We have previously reported that high-density lipoprotein binding protein (HDLBP/vigilin), a multiKH-domain protein, interacts with CTCF and coexists with it at several CTCF-binding sites on the ICR to regulate general gene expression of IGF2. However, the impact of the interaction on imprinting of IGF2 remains unclear. Here, we demonstrate that cooperation of vigilin and CTCF protects IGF2 from losing of imprinting. Pull-down experiments show that KH1-7 domains of vigilin interact with zinc-finger domains of CTCF. We also display that some RNAs participate in the vigilin-CTCF interaction, one of which is H19 long noncoding RNA (lncRNA). Furthermore, we confirm that H19 lncRNA-knockdown alters the imprinting of IGF2. These data suggest that vigilin interacts with CTCF, mediated by H19 lncRNA, to keep the imprinting of IGF2.

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