H3K27me3 may be associated with Oct4 and Sox2 in mouse preimplantation embryos

Abstract

ABSTRACT. As a core member of polycomb repressive complex 2, the transcription and enzyme activity of enhancer of zeste homolog 2 (Ezh2) is directly involved in the trimethylation of lysine 27 on histone H3. In this study, the fluorescence intensity of H3K27me3 in mouse in vivo morulae and blastocysts was compared by indirect immunofluorescence staining. We found that demethylation of H3K27me3 occurred during the blastocyst stage. Real-time polymerase chain reaction was performed to investigate Ezh2 expression in oocytes and in preimplantation embryos. Ezh2 expression peaked during the zygote stage and gradually decreased from the 2-cell stage, exhibiting an inverse pattern when compared with Oct4 and Sox2 mRNA in mouse preimplantation embryos. To understand the role of developmentrelated genes on the transcription of mouse Ezh2, a promoter assay was performed in NIH/3T3 cells. Ezh2 expression was markedly suppressed by Oct4 and Sox2 alone in a dose-dependent manner, while Ezh2 promoter activity in co-transfection with Nanog, Klf-4, and c-Myc groups showed no significant change as compared with the control. Our data suggest that the demethylation of H3K27me3 is caused by the degressive expression and activity of Ezh2 in blastocysts, leading to increased expression of developmentally important transcription factors. We also observed negative effects of Oct4 and Sox2 on the transcription of Ezh2 and identified Oct4 and Sox2 as novel negative regulators of Ezh2 at the post-translation level in a mouse preimplantation embryo.

Loss of tumor suppressor IGFBP4 drives epigenetic reprogramming in hepatic carcinogenesis

“…Intriguingly, these encoded proteins can also interact with the upstream core circuitry. For instance, 11 proteins can bind to AKT, wherein EGFR, AKTIP and RICTOR function as activators ( 31–33 ); and six proteins can interact with EZH2, among which POU5F1 acts as negative regulator ( 34 ) (Figure 6D ). This information supports the notion that additional feedback controls may reinforce the IGFBP4/AKT/EZH2 circuitry.…”

The Effect of Folic Acid Supplementation in the Ovary and Upon Embryo Development

“…However, the synchronised downregulation of Ezh2 and Eed is exclusive to the P.I group, with an increased level of NANOG. EZH2-EED complex has been shown to be regulated by the pluripotency factor OCT4 (Ura et al, 2008;Wu et al, 2014) and depletion of PRC2 core subunit was associated with a delayed embryonic development and a decrease of H3K27me3 (O'Carroll et al, 2001;Hinkins et al, 2005;Huang et al, 2014). Therefore, these results suggest that downregulation of Ezh2 and Eed might induce an upregulation of NANOG through a potential decrease of the repressive mark H3K27me3, allowing the maintenance of the pluripotency state of ICM cells.…”

“…Sox2 are direct targets of EZH2 and EED in ICM and ES cells and with the aim of silencing differentiation factors (Ura et al, 2008;Wu et al, 2014). In contrast to the polycomb repressor genes, no alterations in Dnmts were observed at 3.5dpc in the middle blastocyst stage.…”

“…In embryos, Ezh2 expression peaks during the zygote stage, then gradually decreases from the 2-cell stage, exhibiting an inverse pattern when compared with Oct4 and Sox2. Moreover, further studies showed that Ezh2 expression was markedly suppressed by OCT4 and SOX2 alone in a dose-dependent manner (Wu et al, 2014). EED, also part of PRC2, is required for EZH2 and SUZ12 stability.…”

The Vast Complexity of the Epigenetic Landscape during Neurodevelopment: An Open Frame to Understanding Brain Function

“…After pronuclear membrane formation, some proteins are translocated from oocyte cytoplasm to the pronucleus as EZH2 (Enhancer of Zeste 2 Polycomb repressive complex 2 subunit, a core protein for PRC) that form a complex with histone deacetylases and can repress genetic expression. In fact, Wu et al (2014) showed that decreased EZH2 levels are correlated with the progressive demethylation of H3K27me3, thus allowing the expression of developmentally important transcription factors [ 81 ]. Other enzymes, such as DNMT1o, a form of DNMT1 located at the oocyte, are translocated out of the nucleus, allowing demethylation to occur [ 82 ].…”