The transcriptome of human oocytes

Kocabas, Arif; Crosby, Javier; Ross, Pablo J.; Otu, Hasan H.; Beyhan, Zeki; Can, Handan; Tam, Wai Leong; Rosa, Guilherme J. M.; Halgren, Robert G.; Lim, Bing; Fernández, Emilio; Cibelli, José B.

doi:10.1073/pnas.0603227103

Cited by 178 publications

(135 citation statements)

References 51 publications

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“…In oocytes and preimplantation embryos we detected UTX transcripts only after EGA, in accordance with a previous report in pigs (18), ruling out the possibility that UTX is involved in H3K27me3 decrease during pre-EGA development. In contrast, JMJD3 was highly expressed in bovine GV and MII oocytes, as observed in our reported transcriptome of human MII oocytes (41). After fertilization, JMJD3 mRNA levels decreased significantly.…”

Section: Discussionmentioning

confidence: 55%

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Cánovas

Cibelli

Ross

2012

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the mechanisms of epigenetic remodeling that follow fertilization is a fundamental step toward understanding the bases of early embryonic development and pluripotency. Extensive and dynamic chromatin remodeling is observed after fertilization, including DNA methylation and histone modifications. These changes underlie the transition from gametic to embryonic chromatin and are thought to facilitate embryonic genome activation. In particular, trimethylation of histone 3 lysine 27 (H3K27me3) is associated with gene-specific transcription repression. Global levels of this epigenetic mark are high in oocyte chromatin and decrease to minimal levels at the time of embryonic genome activation. We provide evidence that the decrease in H3K27me3 observed during early development is cell-cycle independent, suggesting an active mechanism for removal of this epigenetic mark. Among H3K27me3-specific demethylases, Jumonji domain-containing protein 3 (JMJD3), but not ubiquitously transcribed tetratricopeptide repeat X (UTX), present high transcript levels in oocytes. Soon after fertilization JMJD3 protein levels increase, concurrent with a decrease in mRNA levels. This pattern of expression suggests maternal inheritance of JMJD3. Knockdown of JMJD3 by siRNA injection in parthenogenetically activated metaphase II oocytes resulted in inhibition of the H3K27me3 decrease normally observed in preimplantation embryos. Moreover, knockdown of JMJD3 in oocytes reduced the rate of blastocyst development. Overall, these results indicate that JMJD3 is involved in active demethylation of H3K27me3 during early embryo development and that this mark plays an important role during the progression of embryos to blastocysts.G amete nuclei undergo extensive chromatin remodeling soon after fertilization, including alterations to DNA methylation levels and posttranslational histone tail modification. These changes are known to influence chromatin structure and transcriptional readout (1) and also to promote embryonic genome activation (EGA) (2), which occurs in humans and cows after three to four cell divisions (3-5). Because the first few cell divisions occur without embryonic gene transcription, maternally inherited mRNA and proteins present in the oocyte are likely responsible for inducing these epigenetic changes (6).Histone lysine methylation is involved in transcriptional repression and/or activation and plays a key role during lineage specification and cell differentiation (7). Di-and trimethylation of histone 3 lysine 27 (H3K27) are catalyzed by the polycomb repressive complex 2 (PRC2), which has three essential components: enhancer of zeste homolog 2 (EZH2), embryonic ectoderm development (EED), and suppressor of zeste 12 (SUZ12) (8-10). These epigenetic marks are specifically associated with gene repression (11) and are typical of many key developmental genes in embryonic stem cells, stem cell maintenance (12-14), and regulation of pluripotency (15). In mouse embryos, asymmetric distribution of trimethylated H3K27 (H3K27me3) i...

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Section: Discussionmentioning

confidence: 55%

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Cánovas

Cibelli

Ross

2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The most highly detrimental situation is probably when the cell tolerates these unrepaired decays-this leads sooner or later to mutations and oncogenic transformation. Fortunately, mammalian cells, including oocytes, have systems that allow DNA repair [12][13][14][15]. DNA repair is probably one of the most important processes taking place during and postfertilization in the oocyte and zygote, in order to allow complete embryonic development and avoid developmental arrests.…”

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confidence: 99%

Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays

Ménézo

Russo

Tosti

et al. 2007

J Assist Reprod Genet

118

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Purpose To determine the level of expression for mRNAs that regulate DNA repair activity in oocytes at the germinal vesicle (GV) stage. Reactive oxygen species (ROS) have been shown to play a major role in the appearance of deleterious DNA decays, and this study focuses on the repair of damage linked to decay caused by the action of ROS. The oocyte needs a mechanism for repairing DNA decays in the early preimplantation embryo before the onset of genomic activation, since in the absence of repair, residual DNA damage would lead to either apoptosis or tolerance. Tolerance of DNA damage is a source of potential mutations. Method GV oocytes were selected for this study, both for the ethical reason that they are unsuitable for patient treatment, and because no transcription takes place during the period from GV to MII and then prior to genomic activation. The GV oocyte is therefore a good model for looking at DNA during the first cleavages of early preimplantation development. Six cohorts of GV oocytes were pooled for extraction of mRNA; the DNA was analysed using Affimetrix HG-UG133 Plus 2, containing 54,675 probe sets; spike and housekeeping genes were also added as internal controls. Results In GV oocytes, DNA repair pathways for oxidized bases are redundant. One step repair procedure (OSR), BER (base excision repair), MMR (mismatch repair) and NER (Nucleotide excision repair) are present. All the recognition proteins are also present. The chromatin assembly factors necessary for the maintenance of genomic stability are highly expressed. Conclusion Gene expression analysis shows that the oocyte does not allow a high level of tolerance for DNA decays. This regulatory mechanism should avoid transmitting mutations into the next generation.

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“…[20][21][22][23] Although gene expression profile data for fetal or neonatal ovaries have been provided in mouse and human, and have enabled the analysis of genes involved in the initiation of meiosis, the sex differentiation of the gonad, early meiosis, and ovarian and follicle development, investigations of meiotic prophase I have been lacking. [24][25][26][27][28] In yeast, it is estimated that B150 genes may be meiosis-specific.…”

Section: Discussionmentioning

confidence: 99%

Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes

et al. 2012

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The events that take place during the prophase of meiosis I are essential for the correct segregation of homologous chromosomes. Defects in these processes likely contribute to infertility or recurrent pregnancy loss in humans. To screen for candidate genes for reproductive failure due to meiotic defects, we have analyzed the gene expression patterns in fetal, neonatal and adult gonads of both male and female mice by microarray and thereby identified 241 genes that are expressed specifically during prophase of meiosis I. Combined with our previous data obtained from developing spermatocytes, a total of 99 genes were identified that are upregulated in early prophase I. We confirmed the meiotic prophase I-specific expression of these genes using qRT-PCR. To further screen this panel for candidate genes that fulfill important roles in homologous pairing, synapsis and recombination, we established a gene transfer system for prophase I oocytes in combination with in vitro organ culture of ovaries, and successfully determined the localization of the selected genes. This gene set can thus serve as a resource for targeted sequence analysis via next-generation sequencing to identify the genes associated with human reproduction failure due to meiotic defects.

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The transcriptome of human oocytes

Cited by 178 publications

References 51 publications

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Jumonji domain-containing protein 3 regulates histone 3 lysine 27 methylation during bovine preimplantation development

Expression profile of genes coding for DNA repair in human oocytes using pangenomic microarrays, with a special focus on ROS linked decays

Screening of genes involved in chromosome segregation during meiosis I: in vitro gene transfer to mouse fetal oocytes

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