Maternal EHMT2 is essential for homologous chromosome segregation by regulating Cyclin B3 transcription in oocyte meiosis.

During oocyte growth, various epigenetic modifications are gradually established, accompanied by accumulation of large amounts of mRNAs and proteins. However, little is known about the relationship between epigenetic modifications and meiotic progression. Here, by using Gdf9-Cre to achieve oocyte-specific ablation of Ehmt2 (Euchromatic-Histone-Lysine-Methyltransferase 2) from the primordial follicle stage, we found that female mutant mice were infertile. Oocyte-specific knockout of Ehmt2 caused failure of homologous chromosome separation independent of persistently activated SAC during the first meiosis. Further studies revealed that lacking maternal Ehmt2 affected the transcriptional level of Ccnb3, while microinjection of exogenous Ccnb3 mRNA could partly rescue the failure of homologous chromosome segregation. Of particular importance was that EHMT2 regulated ccnb3 transcriptions by regulating CTCF binding near ccnb3 gene body in genome in oocytes. In addition, the mRNA level of Ccnb3 significantly decreased in the follicles microinjected with Ctcf siRNA. Therefore, our findings highlight the novel function of maternal EHMT2 on the metaphase I-to-anaphase I transition in mouse oocytes: regulating the transcription of Ccnb3.

PRC2 and EHMT1 regulate H3K27me2 and H3K27me3 establishment across the zygote genome.

The formation of zygote is the beginning of mammalian life, and dynamic epigenetic modifications are essential for mammalian normal development. H3K27 di-methylation (H3K27me2) and H3K27 tri-methylation (H3K27me3) are marks of facultative heterochromatin which maintains transcriptional repression established during early development in many eukaryotes. However, the mechanism underlying establishment and regulation of epigenetic asymmetry in the zygote remains obscure. Here we show that maternal EZH2 is required for the establishment of H3K27me3 in mouse zygotes. However, combined immunostaining with ULI-NChIP-seq (ultra-low-input micrococcal nuclease-based native ChIP-seq) shows that EZH1 could partially safeguard the role of EZH2 in the formation of H3K27me2. Meanwhile, we identify that EHMT1 is involved in the establishment of H3K27me2, and that H3K27me2 might be an essential prerequisite for the following de novo H3K27me3 modification on the male pronucleus. In this work, we clarify the establishment and regulatory mechanisms of H3K27me2 and H3K27me3 in mouse zygotes.

[Historical review of reprogramming and pluripotent stem cell research in China].

The research of stem cell field has developed rapidly in recent decades. With the enhancing of China's economic power, the strength of scientific research is steadily increasing, and the stem cell research even has reached international advanced level. Here, we make a historical review of important research in China, focusing on somatic cell nuclear transfer, induced pluripotent stem cells, haploid pluripotent stem cells and early embryo development. The fast development of single cell sequencing will greatly help the understanding of various development process, and the stem cell clinical application will blossom in China in the future.

Clinical observation on recombinant human endostatin combined with chemotherapy for advanced gastrointestinal cancer.

OBJECTIVE: To explore the clinical efficacy and toxic and side effects of recombinant human endostatin (rh- endostatin/endostar) combined with chemotherapy in the treatment of advanced gastric cancer. MATERIALS AND METHODS: A total of 70 patients with advanced gastrointestinal adenocarcioma confirmed by histopathology and/or cytological examination were divided into group A (37 patients) and group B (33 patients). Patients in group A were given intravenous drip of 15 mg endostar added into 500 mL normal saline, once every other day until the cessation of chemotherapy or patients' maximal tolerance to chemotherapy. Patients in group B received chemotherapy alone. Two groups selected the same chemotherapy regimens. FOLFIRI scheme: 90-min intravenous drip of 180 mg/m2 irinotecan, intravenous drip of 200 mg/m2 calcium folinate (CF) and 400 mg/m2 5-fluorouracil (5-Fu) on d1, and continuous intravenous pumping of 2 400 mg/m2 5-Fu for 46 h. FOLFOX4 scheme: intravenous injection of 85 mg/m2 oxaliplatin (L-OHP), 200 mg/m2 calcium folinate (CF) and 400 mg/m2 5-FU on d1 for 2 h, and then continuous intravenous pumping of 2 400 mg/m2 5-Fu for 46 h. XELOX scheme: oral administration of 1 500 mg/m2 xeloda (or tegafur 50~60 mg) in twice during d1~14 and intravenous drip of 135 mg/m2 L-OHP on d1 for 2 h. The modified FOLFOX scheme: intravenous injection of 135 mg/m2 L-OHP on d1 for 2 h, 200 mg/m2 CF and 1.0 g tegafur during d1~5. Whereas, control Group B received chemotherapy regimens which were same as Group A, but no addition of endostar. Before chemotherapy, patients were given intravenous injection of 8 mg ondansetron, intramuscular injection of 10 mg metoclopramide and 20 mg diphenhydramine for prevention of vomiting, protection of liver and stomach as well as symptomatic supportive treatment. One cycle was 21 d, 4~6 cycles in total. The efficacy was evaluated every 2 cycles. RESULTS: 32 patients in Group A could be evaluated, and the response rate (RR) and disease control rate (DCR) were 59.38% and 78.13%, respectively. 31 patients in Groups could be evaluated, and the RR and DCR were 32.26% and 54.84%, respectively. The differences between 2 groups were significant. The toxic effects include myelosuppression, gastrointestinal reaction, fatigue, cardiotoxicity and peripheral neurotoxicity. CONCLUSIONS: Preliminary observations show that endostar (once every other day) combined with chemotherapy is effective in the treatment of advanced gastrointestinal cancer, with low toxic effects, good tolerance, deserving further study.