Eif2s2 deficiency causes oocyte arrest at the early diplotene stage and apoptosis in mice
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ABSTRACT:
PROVIDER: PRJNA1099574 | ENA |
REPOSITORIES: ENA
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Project description:Mutations in translation initiation factors are associated with premature ovarian insufficiency. Here, we used signle-cell RNA sequencing method to investigate the effect of Eif2s2 deletion in premeiotic germ-cells on primordial formation.
2024-12-18 | GSE263836 | GEO
Project description:HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge [oocyte-transcriptome]
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Project description:In response to stress, the p53 tumor suppressor induces arrest or apoptosis by transcriptionally regulating genes that mediate these processes. It has been proposed that the levels of p53 can influence the choice between these different outcomes, but the mechanisms involved are not clear. To gain mechanistic understanding of this p53-dependent cell fate decision, we generated a p53 inducible system that allowed tight regulation of p53 expression in human mammary epithelial cells. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Using microarray and chromatin immunoprecipitation analysis, we showed that low and high levels of p53 bind to and activate the same set of pro arrest and pro apoptotic target genes, induced to lower and higher levels, respectively. We propose that the cell fate decision between arrest and apoptosis in these cells is determined by a higher threshold required for p53 dependent apoptosis. We suggest that high level p53 activation is crucial in order to achieve maximum efficacy of p53 targeted cancer therapies.
2011-07-19 | E-GEOD-30753 | biostudies-arrayexpress
Project description:Fluorinated rhodacyanines induce apoptosis via mitochondrial damage and cell cycle arrest
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Project description:HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge
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Project description:Lip-1 induces cell cycle arrest, apoptosis, and pyroptosis in K562 cells
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Project description:Dramatic changes in chromatin structure and histone modification occur during oocyte growth, as well as a global cessation of transcription. The role of histone modifications in these processes is poorly understood. We report the effect of conditionally deleting Hdac1 and Hdac2 on oocyte development. Deleting either gene has little or no effect on oocyte development, whereas deleting both genes results in follicle development arrest at the secondary follicle stage. This developmental arrest is accompanied by substantial perturbation of the transcriptome and a global reduction in transcription even though histone acetylation is markedly increased. There is no apparent change in histone repressive marks but there is a pronounced decrease in histone H3K4 methylation, an activating mark. The decrease in H3K4 methylation is likely due to increased expression of Kdm5b because RNAi-mediated targeting of Kdm5b in double mutant oocytes results in an increase in H3K4 methylation. An increase in TRP53 acetylation also occurs in mutant oocytes and may contribute to the observed increased incidence of apoptosis. Taken together, these results suggest seminal roles of acetylation of histone and non-histone proteins in oocyte development. We used microarrays to detail the global programme of gene expression underlying oocyte development and identified distinct classes of regulated genes during this process.
2011-12-31 | GSE34786 | GEO
Project description:Dramatic changes in chromatin structure and histone modification occur during oocyte growth, as well as a global cessation of transcription. The role of histone modifications in these processes is poorly understood. We report the effect of conditionally deleting Hdac1 and Hdac2 on oocyte development. Deleting either gene has little or no effect on oocyte development, whereas deleting both genes results in follicle development arrest at the secondary follicle stage. This developmental arrest is accompanied by substantial perturbation of the transcriptome and a global reduction in transcription even though histone acetylation is markedly increased. There is no apparent change in histone repressive marks but there is a pronounced decrease in histone H3K4 methylation, an activating mark. The decrease in H3K4 methylation is likely due to increased expression of Kdm5b because RNAi-mediated targeting of Kdm5b in double mutant oocytes results in an increase in H3K4 methylation. An increase in TRP53 acetylation also occurs in mutant oocytes and may contribute to the observed increased incidence of apoptosis. Taken together, these results suggest seminal roles of acetylation of histone and non-histone proteins in oocyte development. We used microarrays to detail the global programme of gene expression underlying oocyte development and identified distinct classes of regulated genes during this process. Total RNA was extracted from 80 oocytes isolated from mice 12 days-of-age using the PicoPure RNA kit (Arcturus), amplified with the Ovation Pico WTA system (NuGen), and then fragmented and labeled with the FL-OvationTM cDNA Biotin Module V2 (NuGen). Four independent biological replicates were hybridized to Affymetrix GeneChip Mouse 1.1 ST microarrays (http://www.affymetrix.com/). Raw microarray data were analyzed as previously described using MAS5, GeneSpring v7, SAM and EASE software (56). A 1.4-fold cutoff was used for EASE analysis; four biological replicates provide sufficient statistical power and confidence to detect a 1.4-fold change in transcript abundance
2011-12-31 | E-GEOD-34786 | biostudies-arrayexpress
Project description:Mammalian oocyte meiosis is a special form of cell division that provides haploid gametes for fertilization. Unlike in mitosis, post-translational modifications (PTMs) are more crucial during meiosis because of the absence of de novo mRNA transcription. As a classic PTM, protein neddylation is a biological process that mediates protein degradation by modifying cullin proteins and activating the Cullin-Ring E3 ligases. This process plays important roles in various biological processes such as autophagy and tumorigenesis. However, the function of neddylation in germ cells is unknown. In this study, we observed that the inhibition of neddylation by its specific inhibitor MLN4924 significantly arrests mouse oocyte at the stage of metaphase during meiosis. The arrested oocytes display impaired spindles with over-activation of spindle assembly checkpoint (SAC). Accordingly, we identified early mitosis inhibitor 1 (Emi1), a key inhibitor of anaphase-promoting complex/cyclosome (APC/CFzr1), as a substrate of neddylation-mediated protein degradation. Thus, our study uncovered an unknown role of neddylation in female germ cells and suggests that proper neddylation is essential for oocyte maturation.
| S-EPMC6592254 | biostudies-literature
Project description:The genetic causes of oocyte meiotic deficiency (OMD), a form of primary infertility characterised by the production of immature oocytes, remain largely unexplored. Using whole exome sequencing, we found that 26% of a cohort of 23 subjects with OMD harboured the same homozygous nonsense pathogenic mutation in PATL2, a gene encoding a putative RNA-binding protein. Using Patl2 knockout mice, we confirmed that PATL2 deficiency disturbs oocyte maturation, since oocytes and zygotes exhibit morphological and developmental defects respectively. PATL2's amphibian orthologue is involved in the regulation of oocyte mRNA as a partner of CPEB. However, Patl2's expression profile throughout oocyte development in mice, alongside colocalisation experiments with Cpeb1, Msy2 and Ddx6 (three oocyte RNA-regulators) suggest an original role for Patl2 in Mammals. Accordingly, transcriptomic analysis of oocytes from WT and Patl2-/- animals demonstrated that in the absence of Patl2, expression levels of a select number of highly relevant genes involved in oocyte maturation and early embryonic development are deregulated. In conclusion, PATL2 is a novel actor of mammalian oocyte maturation whose invalidation causes OMD in humans.
| EGAS00001002903 | EGA