Nanog positively regulates Zfp57 expression in mouse embryonic stem cells

Abstract

a b s t r a c tTo maintain the self-renewal of embryonic stem (ES) cells, several core transcription factors, including Oct3/4, STAT3, and Nanog, regulate the expression of their target genes. Zinc finger protein 57 (Zfp57) is specifically expressed in self-renewing ES cells and its expression level is reduced upon ES cell differentiation, suggesting that expression of this transcription factor is regulated by core transcription factors. In the present study, we investigated whether Zfp57 expression is regulated by Nanog. Nanog overexpression resulted in the upregulation of Zfp57. On the other hand, knockdown of Nanog reduced the expression level of Zfp57. In addition, we identified the Nanog-responsive region in the promoter of the Zfp57 gene. These results suggest that Nanog is an upstream regulator of Zfp57. Moreover, Nanog overexpression promoted the growth of ES cells in soft agar and this was suppressed by Zfp57 knockdown, suggesting that the Nanog/Zfp57 pathway plays a central role in anchorage-independent growth of ES cells. Interestingly, NANOG overexpression also led to the upregulation of ZFP57 in two human tumor cell lines. Taken together, our results suggest that Nanog positively regulates Zfp57 expression in multiple types of cells.

Platelet-derived growth factor-C functions as a growth factor in mouse embryonic stem cells and human fibrosarcoma cells

“…These results suggest that PDGF-C is involved in anchorage-dependent growth of ES cells. ES cells can grow under anchorage-independent conditions [17,29], as expected since they can give rise to benign tumors called teratomas when injected into immunodeficient mice [30]. The PDGF-R inhibitor AG1296 suppressed anchorageindependent growth of E14 ES cells in soft agar (Fig.…”

KRAB-ZFPs and cancer stem cells identity

“… 151 Indeed, Nanog may participate in the upregulation of Zfp57 as demonstrated in mESCs. 152 Moreover, ZFP57 upregulation correlated with poorer patient outcome. 151 Altogether, these observations suggest ZFP57 may play a role in the maintenance and proliferation of CSCs.…”

“…Zfp57 was also demonstrated to influence the anchorage-independent growth of mESCs – knock-down of Zfp57 with simultaneous Nanog overexpression resulted in a reduction in the number of cell colonies. 152 Higher expression of ZFP57 is thus associated with a greater proliferation potential of ESCs. Moreover, an increased expression of ZFP57 was also observed in grade IV compared to grade II glioblastoma.…”

Review of Environmental Impact on the Epigenetic Regulation of Atopic Diseases

“…A study in human cohort showed that maternal folate intake caused hypomethylation of zinc finger protein 57 (ZFP57) transcripts, a master regulator of DNA methylation [94]. In addition to DNA methylation, histone acetylation H3 and H4 were also altered by maternal folate intake and was associated with high mRNA expression in CD41 T cells [95].…”