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Comment |
Investigating the potential of genes preferentially expressed in oocyte to induce chromatin remodeling in somatic cells. Sylvestre EL et al. The oocyte capacity to rejuvenate a differentiated nucleus to restart the proper embryonic program has been highly conserved between vertebrate species. In view of the recent progress to induce pluripotency in somatic cells with stemness genes, we investigated the potential of oocyte genes to contribute to chromatin rearrangements in somatic cells. We selected conserved genes that are naturally expressed mainly in oocytes and that were susceptible to play a role in reprogramming during early embryogenesis. We induced their expression by transient transfection in HEK293?cells. We then assessed whether they had a global impact on epigenetic events such as histone core modifications, and also on transcription and expression of pluripotency-associated transcription factors. Nucleoplasmin 2 (NPM2), activation-induced cytidine deaminase (AICDA), and Geminin (GMNN) overexpression induced differences in histone core modifications (methylation and acetylation). AICDA and NPM2 also influenced RNA neosynthesis. NPM2, GMNN, and STELLA induced overexpression of well-known pluripotency transcription factors. Overall, AICDA, GMNN, NPM2, and STELLA influenced at least one of the aspects analyzed. Their potential could be useful in increasing the cell receptivity to pluripotency induction.
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Mutations |
2 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: None
Comment: Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development. Gonzalez MA et al. In multicellular eukaryotes, geminin prevents overreplication of DNA in proliferating cells. Here, we show that genetic ablation of geminin in the mouse prevents formation of inner cell mass (ICM) and causes premature endoreduplication at eight cells, rather than 32 cells. All cells in geminin-deficient embryos commit to the trophoblast cell lineage and consist of trophoblast giant cells (TGCs) only. Geminin is also down-regulated in TGCs of wild-type blastocysts during S and gap-like phases by proteasome-mediated degradation, suggesting that loss of geminin is part of the mechanism regulating endoreduplication.
Species: mouse
Mutation name:
type: null mutation
fertility: infertile - ovarian defect
Comment: Geminin Deletion in Mouse Oocytes Results in Impaired Embryo Development and Reduced Fertility. Ma XS et al. (2016) Geminin controls proper centrosome duplication, cell division and differentiation. We investigated the function of geminin in oogenesis, fertilization and early embryo development by deleting geminin gene in oocytes from primordial follicle stage. Oocyte-specific disruption of geminin results in low fertility in mice. Even though there was no evident anomaly of oogenesis, oocyte meiotic maturation, natural ovulation and fertilization, early embryo development and implantation were impaired. The fertilized eggs derived from mutant mice showed development delay, and many were blocked at the late zygote stage. Cdt1 protein was decreased, while Chk1 and H2AX phosphorylation was increased in fertilized eggs after geminin depletion. Our results suggest that disruption of maternal geminin may decrease Cdt1 expression and cause DNA rereplication, which then activates the cell cycle checkpoint and DNA damage repair, and thus impairs early embryo development.//////////////////
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