Browsing by Subject "Epigenetics"
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- PublicationOpen AccessEffect of Superovulation Treatment on Oocyte's DNA Methylation(MDPI, 2022-12-18) S. Lopes, Jordana; Ivanova, Elena; Ruiz, Salvador; Andrews, Simon; Kelsey, Gavin; Coy, Pilar; Didáctica y Organización EscolarControlled ovarian stimulation is a necessary step in some assisted reproductive procedures allowing a higher collection of female gametes. However, consequences of this stimulation for the gamete or the offspring have been shown in several mammals. Most studies used comparisons between oocytes from different donors, which may contribute to different responses. In this work, we use the bovine model in which each animal serves as its own control. DNA methylation profiles were obtained by single-cell whole-genome bisulfite sequencing of oocytes from pre-ovulatory unstimulated follicles compared to oocytes from stimulated follicles. Results show that the global percentage of methylation was similar between groups, but the percentage of methylation was lower for non-stimulated oocytes in the imprinted genes APEG3, MEG3, and MEG9 and higher in TSSC4 when compared to stimulated oocytes. Differences were also found in CGI of imprinted genes: higher methylation was found among non-stimulated oocytes in MEST (PEG1), IGF2R, GNAS (SCG6), KvDMR1 ICR UMD, and IGF2. In another region around IGF2, the methylation percentage was lower for non-stimulated oocytes when compared to stimulated oocytes. Data drawn from this study might help to understand the molecular reasons for the appearance of certain syndromes in assisted reproductive technologies-derived offspring.
- PublicationOpen AccessEffect of superovulation treatment on oocyte´s DNA methylation.(MDPI, 2022-12-18) Lopes, J.S.; Ivanova, E.; Ruiz, S.; Andrews, S.; Kelsey, G.; Coy, P.; Fisiología; Epigenetics Programme. Babraham Institute. Cambridge, U.K.; Bioinformatics Group. Babraham Institute. Cambridge, U.K.; Centre for Trophoblast Research. Cambridge University. U.K.Controlled ovarian stimulation is a necessary step in some assisted reproductive procedures allowing a higher collection of female gametes. However, consequences of this stimulation for the gamete or the offspring have been shown in several mammals. Most studies used comparisons between oocytes from different donors, which may contribute to different responses. In this work, we use the bovine model in which each animal serves as its own control. DNA methylation profiles were obtained by single-cell whole-genome bisulfite sequencing of oocytes from pre-ovulatory unstimulated follicles compared to oocytes from stimulated follicles. Results show that the global percentage of methylation was similar between groups, but the percentage of methylation was lower for non-stimulated oocytes in the imprinted genes APEG3, MEG3, and MEG9 and higher in TSSC4 when compared to stimulated oocytes. Differences were also found in CGI of imprinted genes: higher methylation was found among non-stimulated oocytes in MEST (PEG1), IGF2R, GNAS (SCG6), KvDMR1 ICR UMD, and IGF2. In another region around IGF2, the methylation percentage was lower for non-stimulated oocytes when compared to stimulated oocytes. Data drawn from this study might help to understand the molecular reasons for the appearance of certain syndromes in assisted reproductive technologies-derived offspring.
- PublicationOpen AccessGASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Uimonen, Katri; Merikallio, Heta; Pääkkö, Paavo; Harju, Terttu; Mannermaa, Arto; Palvimo, Jorma; Kosma, Veli-Matti; Soini, YlermiGASC1 (gene amplified in squamous cell carcinoma 1) encodes a nuclear protein that epigenetically catalyses the lysine demethylation of histones. We investigated the expression of GASC1 in different histological subtypes of lung cancer (n=289). Percentage value of GASC1 immunohistochemical expression was evaluated separately in the nuclei and cytoplasms of epithelial cancer cells. The results were compared with clinicopathologic factors and the smoking history of the patients. In lung tumor cells, 38% of nuclei and 54% of the cytoplasms stained positive for GASC1. Adenocarcinomas expressed more GASC1 nuclear (p=0.00011) and cytoplasmic (p=0.00074) positivity than squamous cell carcinoma. Smokers displayed less nuclear and cytoplasmic GASC1 expression than non-smokers (p=0.028 and p=0.036, respectively). Similarly, patients with more cytoplasmic positive staining had fewer pack years (p=0.043). Nuclear GASC1 expression had an impairing effect on survival when all histological lung cancer types were analysed together (p=0.039) and separately in squamous cell lung carcinoma (p=0.016). The results reveal that GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. Nonetheless, nuclear GASC1 predicts a poor prognosis, especially in squamous cell carcinoma.
- PublicationEmbargoInduction and stability of the anergic phenotype in T cells(2013-11-15) Valdor, Rut; Macián, Fernando; Bioquímica y Biología Molecular B e InmunologíaOne of the mechanisms that are in place to control the activation of mature T cells that bear self-reactive antigen receptors is anergy, a long-term state of hyporesponsiveness that is established in T cells in response to suboptimal stimulation. T cells receive signals that result not only from antigen recognition and costimulation but also from other sources, including cytokine receptors, inhibitory receptors or metabolic sensors. Integration of those signals will determine T cell fate. Under conditions that induce anergy, T cells activate a program of gene expression that leads to the production of proteins that block T cell receptor signaling and inhibit cytokine gene expression. In this review we will examine those signals that determine functional outcome following antigen encounter, review current knowledge of the factors that ensure signaling inhibition and epigenetic gene silencing in anergic cells and explore the mechanisms that lead to the reversal of anergy and the reacquisition of effector functions
- PublicationOpen AccessSingle-cell DNA methylation sequencing reveals epigenetic alterations induced by bovine oocyte in vitro maturation(Brazilian College of Animal Reproduction, 2024-06-28) Abril-Parreño, Laura; Lopes, Jordana S.; Romero-Aguirregomezcorta, Jon; Galvao, Antonio; Kelsey, Gavin; Coy, Pilar; Fisiología; Facultad de VeterinariaOocyte in vitro maturation (IVM) is a key step for the in vitro production of bovine embryos. However, there is a concern that this process may induce suboptimal developmental competence of bovine oocytes including epigenetic alterations. Currently, epigenetic profile of bovine oocyte IVM is relatively limited and inconsistent, probably arising from differences in the detection approach and experimental design used between studies. The aim of this work was to determine whether DNA methylome alterations are present in bovine oocytes that were in vitro matured and to identify conserved biomarkers across species. To achieve this, the results of this study were compared to those obtained in a similar study with in vitro matured porcine oocytes (unpublished data). The study was performed on 18 in vitro matured oocytes recovered from 2-8 mm follicles of abattoir-derived bovine ovaries and 28 in vivo matured oocytes collected by ovum-pick-up. Transvaginal aspiration was performed at 96–98 h after GnRH administration. The analysis of DNA methylation was performed by single-cell whole-genome bisulphite sequencing. Then, differentially methylated regions (DMRs, FDR < 0.05, FC > 0.1) were determined using the R package limma. Results showed that global DNA methylation profiles differed between in vitro and in vivo groups. Individual oocytes were clustered using Uniform Manifold Approximation and Projection analysis, which showed a clear separation within the in vivo group according to breed and age. The analysis of DMR identified a lower number of hypermethylated and hypomethylated regions in the IVM group, which were more frequent in variably methylated regions (VMRs), promoters, transcripts and imprinted genes. No differences were found in methylation of CpG islands of genes previously related to large offspring syndrome between groups. Regarding the effect on genomic imprinting, methylation was lower for IVM oocytes in the imprinted gene CDKN1C and higher in the BEGAIN gene when compared to the in vivo group. In addition, the analysis of genes that have been previously predicted for their possible function in the imprinting process showed a number of differences between the in vivo and in vitro group. For example, we identified lower methylation in in vitro matured oocytes in CpG islands of 5 “candidate” genes (SEMA7A, ZNF575, ATP4B, PDGFA, COMP) while only one was hypermethylated in the coding region of the PLCL2 gene. Finally, we identified conserved differences in methylation related to IVM between bovine and porcine oocytes for 14, 8 and 3 genomic features in the transcripts, VMRs and promoters, respectively. The findings indicate that some of the epigenetic alterations are associated with suboptimal developmental competence of IVM oocytes. In conclusion, these results could help to improve this technique when employing in vitro production procedures in cattle.
- PublicationOpen AccessTranscriptional regulation of the Oct4 gene, a master gene for pluripotency(Murcia : F. Hernández, 2010) Kellner, Steven; Kikyo, NobuakiOct4 is one of the most importanttranscription factors required to maintain anundifferentiated state (self-renewal) and pluripotency ofhuman and mouse embryonic stem (ES) cells as well asearly embryonic cells. In addition, Oct4 is the onlyknown transcription factor that has to be exogenouslyintroduced into differentiated cells to make inducedpluripotent stem (iPS) cells. Therefore, it is of greatimportance to understand howOct4transcription isregulated in ES cells and embryos and how it becomesactivated during iPS cell formation. In this article, wewill review the regulation of the mouse Oct4gene fromthe viewpoint of DNA methylation, binding of orphannuclear receptors, histone modifications and synergisticeffects with other pluripotency factors. We will also raiseseveral key questions that need to be addressed in futurework to improve our understanding of Oct4generegulation and its essential role in self-renewal andpluripotency.