EZH can also interact with Ten

EZH2 can also interact with Ten-Eleven Translocation gene family members (TET1, TET2, and TET3), which convert 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5hmC), to cause changes in patterns of histone methylation and DNA methylation [52]. Huang et al. found that the expression levels of all the TETs members were increased in porcine blastocysts after knockdown of KDM5B, a demethylase of H3K4me3 [37]. Intriguingly, we observed that the production of TET2 and TET3 was increased while that of TET1 was remarkably down-regulated after EZH2 knockdown, indicating that each of the three may have its own particular function besides converting 5 mC into 5hmC. Studies in porcine preimplantation embryos have identified that the conversion of 5 mC to 5- 5hmC is dynamic during vitamin d3 sources development, and is mainly regulated by TET3 at the initial stage and by TET1 at the later stage. Notably, the expression of NANOG was significantly decreased after TET3 knockdown at the zygote stage [53]. It is also documented that TET1 co-localizes with PRC2, and EZH2 has been identified as a co-factor of TET1 in controlling DNA methylation [52,54]. Furthermore, Tet1 is required for ES cell maintenance and preferentially binds to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes [29]. Knockdown of Tet1 in pre-implantation embryos results in a bias towards trophectoderm differentiation and the downregulation of Nanog due to the methylation of the Nanog promoter [55]. This is consistent with our observation that knockdown of EZH2 resulted in the downregulation of TET1 and pluripotency factors such as NANOG and the increase of GATA3, a marker of trophoderm. This may also contribute to the impaired competency of embryonic development.
Conclusion We presented data that the expression of EZH2 is stage specific and is consistent with the dynamic change of H3K27me3 during preimplantation parthenogenetic development. Depletion of EZH2 caused a lower developmental capacity and a decreased quality of blastocysts, which may result from the disturbed bivalent balance of H3K27me3 and H3K4me3 in the EZH2 knockdown embryos. The downregulation of NANOG and the upregulation of GATA3 might be induced indirectly, given that the expression of TET1 is decreased. Together with changes in the expression of pluripotency related genes OCT4 and SOX2, differentiation related genes and apoptosis-associated genes, these findings are reasonable, in a way, to propose that EZH2 interacts with different complexes to get involved in the mechanisms underlying cell self-renewal, differentiation initiation and apoptosis in pig early parthenogenetic embryos.
Author contributions
Declaration of interest
Role of the funding source
Acknowledgments We thank Yueting Zhang for her assistance in collecting ovaries and selecting cumulus-oocyte complexes. This work was supported by National Transgenic Major Program (2016ZX08006003-006).
Introduction Lung cancer, one of the most common cancers worldwide, remains the leading cause of death from cancer. There were 226,160 new cases of lung cancer and 160,340 cases of lung cancer deaths in 2012 [39]. With a lower early diagnosis rate of lung cancer, lung cancer is mostly diagnosed in the high metastasis stage of the tumour and is difficult to cure, with a poor prognosis [32]. The survival rate of lung cancer within 5 years is approximately 15% [21]. Moreover, lung adenocarcinoma is a main subtype of lung cancer with a poor chemotherapeutic effect, and a large number of patients show resistance to cisplatin [33]. Due to the lower early diagnosis rate, limited chemotherapeutic effect, and poor prognosis of lung adenocarcinoma, biomarkers with high sensitivity and specificity would be helpful in identifying its pathological changes, and new biomarkers would predict prognosis and provide a specific treatment strategy for lung adenocarcinoma to obtain better clinical outcomes.