The role of GRHL2 and epigenetic remodeling in epithelial–mesenchymal plasticity in ovarian cancer cells
| العنوان: | The role of GRHL2 and epigenetic remodeling in epithelial–mesenchymal plasticity in ovarian cancer cells |
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| المؤلفون: | Tuan Zea Tan, Heike Wollmann, Rui Lan Huang, Jieru Ye, Vin Yee Chung, Ernesto Guccione, Ruby Yun-Ju Huang, Hung Cheng Lai, Dennis Kappei |
| المصدر: | Communications Biology, Vol 2, Iss 1, Pp 1-15 (2019) Communications Biology |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Epithelial-Mesenchymal Transition, Cell, Medicine (miscellaneous), Biology, General Biochemistry, Genetics and Molecular Biology, Article, Epigenesis, Genetic, Histones, Ovarian cancer, Cell Line, Tumor, medicine, Humans, Epigenetics, lcsh:QH301-705.5, Ovarian Neoplasms, Gene knockdown, DNA Methylation, Cell biology, DNA-Binding Proteins, medicine.anatomical_structure, Histone, CpG site, lcsh:Biology (General), Differentiation, Gene Knockdown Techniques, DNA methylation, Cancer cell, biology.protein, H3K4me3, CpG Islands, Female, General Agricultural and Biological Sciences, Transcription Factors |
| الوصف: | Cancer cells exhibit phenotypic plasticity during epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET) involving intermediate states. To study genome-wide epigenetic remodeling associated with EMT plasticity, we integrate the analyses of DNA methylation, ChIP-sequencing of five histone marks (H3K4me1, H3K4me3, H3K27Ac, H3K27me3 and H3K9me3) and transcriptome profiling performed on ovarian cancer cells with different epithelial/mesenchymal states and on a knockdown model of EMT suppressor Grainyhead-like 2 (GRHL2). We have identified differentially methylated CpG sites associated with EMT, found at promoters of epithelial genes and GRHL2 binding sites. GRHL2 knockdown results in CpG methylation gain and nucleosomal remodeling (reduction in permissive marks H3K4me3 and H3K27ac; elevated repressive mark H3K27me3), resembling the changes observed across progressive EMT states. Epigenetic-modifying agents such as 5-azacitidine, GSK126 and mocetinostat further reveal cell state-dependent plasticity upon GRHL2 overexpression. Overall, we demonstrate that epithelial genes are subject to epigenetic control during intermediate phases of EMT/MET involving GRHL2. Vin Yee Chung et al. identify differentially methylated CpG sites in the promoters of epithelial genes and GRHL2 binding sites in ovarian cancer cells during the epithelial–mesenchymal transition. They find that GRHL2 knockdown or overexpression affects methylation, suggesting a role for this transcription factor in epigenetic remodeling. |
| اللغة: | English |
| تدمد: | 2399-3642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ce61b3a08a84559e4af8bdb920b6628 http://link.springer.com/article/10.1038/s42003-019-0506-3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9ce61b3a08a84559e4af8bdb920b6628 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23993642 |
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