Mouse ZFP57 peptide

Several common biological properties between cancer cells and embryonic stem (ES) cells suggest the possibility that some genes expressed in ES cells might have important roles in cancer cell growth. The transcription factor ZFP57 is expressed in self-renewing ES cells and its expression level decreases during ES cell differentiation. This study showed that ZFP57 is involved in the anchorage-independent growth of human fibrosarcoma HT1080 cells in soft agar. ZFP57 overexpression enhanced, whereas knockdown suppressed, HT1080 tumor formation in nude mice. Furthermore, ZFP57 regulates the expression of insulin-like growth factor 2 (IGF2), which has a critical role in ZFP57-induced anchorage-independent growth. ZFP57 also promotes anchorage-independent growth in ES cells and immortal fibroblasts. Finally, immunohistochemical analysis revealed that ZFP57 is overexpressed in human cancer clinical specimens. Taken together, these results suggest that the ES-specific transcription factor ZFP57 is a novel oncogene.

DNA methylation is an essential epigenetic modification involved in regulating gene expression and maintaining epigenetic information across generations. However, how these marks are recognized and interpreted to activate or repress imprinted genes is not fully understood. Preliminary evidence describes the transcriptional repressor TRIM28 as a key regulator of imprinted gene expression during and after early genome-wide reprogramming. Aberrant expression of imprinted genes maybe one possible cause of incomplete epigenetic reprogramming and low efficiency in somatic cell nuclear transfer. Here, we perform a series of experiments to determine whether knockdown of Tritn28 alters imprinted gene expression and DMR methylation in sheep embryonic fibroblast (SEF) cells. siRNA-mediated Trim28 silencing in SEF cells resulted in significantly decreased expression of Gt12 to 30% and increased expression of Dlkl (-1.7-fold). Moreover, knocking down Trim28 induced DNA methylation at the IG-DMR and the Gt12 promoter was disrupted. Here, we uncover an important role for Trim28 in the maintenance of DNA methylation at IG-DMR during replication-dependent dilution of methylated cytosine during cellular proliferation. Unlike Dlk1-Gt12 however, knocking down Trim28 does not affect DMR methylation in the Igf2-H19 gene cluster, yet results in increased expression of Igf2 and H19. Interestingly, Peg3 expression decreased by 60% in Trim28 knockdown cells. PEG3 as a transcriptional repressor to the H19-ICR that interacts with the co-repressor protein TRIM28 through KRAB-A. Trim28 therefore appears to control the Igf2-H19 imprinted cluster indirectly via PEG3, which is distinct from its classical role in preserving DNA methylation during DNA replication. Our results therefore indicate that Trim28 regulates imprinted gene expression through at least two distinct mechanisms during cells proliferation.