The Maternal Effect Genes UTX and JMJD3 Play Contrasting Roles in Mus musculus Preimplantation Embryo Development

Abstract

During the process of embryonic development in mammals, epigenetic modifications must be erased and reconstructed. In particular, the trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcriptional repression and contributes to the maintenance of the pluripotent embryos. In this study, we determined that the global levels of the H3K27me3 marker were elevated in MII oocyte chromatin and decrease to minimal levels at the 8-cell and morula stages. When the blastocyst hatched, H3K27me3 was re-established in the inner cell mass. We also determined that H3K27me3-specific demethylases, UTX and JMJD3, were observed at high transcript and protein levels in mouse preimplantation embryos. In the activated oocytes, when the H3K27me3 disappeared at the 8-cell stage, the UTX (but not JMJD3) protein levels were undetectable. Using RNA interference, we suppressed UTX and JMJD3 gene expression in the embryos and determined that the functions of UTX and JMJD3 were complementary. When JMJD3 levels were decreased by RNA interference, the embryo development rate and quality were improved, but the knockdown of UTX produced the opposite results. Understanding the epigenetic mechanisms controlling preimplantation development is critical to comprehending the basis of embryonic development and to devise methods and approaches to treat infertility.

KDM 6A and KDM 6B play contrasting roles in nuclear transfer embryos revealed by MERVL reporter system

“…Previous studies have shown that the knockdown of KDM6B or overexpression of KDM6A in MEFs results in significantly more iPSC colonies compared with wild-type cells [55,56]. Interestingly, the knockdown of KDM6B in SCNT embryos leads to a moderate increase in the expression of KDM6A, consistent with our previous findings in mouse parthenogenetic embryos [41]. While our paper was under preparation, another study reported the identification of H3K27me3-dependent imprinting genes (which include Gab1, Sfmbt2, and Slc38a4), and previous studies have shown that these genes exhibit a loss of imprinting in SCNT embryos [57,58].…”

“…As described above, the ectopic overexpression of KDM6A mRNA at low concentrations improved the SCNT efficiency. We have previously shown that mouse parthenogenetic embryos in which KDM6B is knocked down exhibited a moderate increase in KDM6A expression . We speculated that KDM6B knockdown could facilitate ZGA and improve SCNT efficiency.…”

Fine Tuning of Histone Demethylase KDM6A/B Improves the Development of Nuclear Transfer Embryo

“…Previous studies have shown that the knockdown of KDM6B or over-expression of KDM6A in MEFs results in significantly more iPSC colonies compared with wild-type cells [56, 57]. Interestingly, the knockdown of KDM6B in SCNT embryos leads to a moderate increase in the expression of KDM6A, consistent with our previous findings in mouse parthenogenetic embryos [42]. While our paper was under preparation, another study reported the identification of H3K27me3-dependent imprinting genes (which include Gab1, Sfmbt2 and Slc38a4) , and previous studies have shown that these genes exhibit a loss of imprinting in SCNT embryos [58, 59].…”

“…As described above, the ectopic overexpression of KDM6A mRNA at low concentrations improved the SCNT efficiency. We have previously shown that mouse parthenogenetic embryos in which KDM6B is knocked down exhibited a moderate increase in KDM6A expression [42]. We speculated that KDM6B knockdown could facilitate ZGA and improve SCNT efficiency.…”

“…Chemicals were purchased from Sigma Chemical Co. (USA) unless otherwise indicated. Superovulation was done as previously described [42]. Briefly, BDF1 female (6 ~ 8 weeks old) mice were superovulated by intraperitoneal injection of pregnant mare serum gonadotropin (PMSG; Sansheng, China, 10 IU) and human chorionic gonadotropin (hCG; Sansheng, China, 10 IU) 48 h apart.…”