Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes
| العنوان: | Global mapping of DNA methylation in mouse promoters reveals epigenetic reprogramming of pluripotency genes |
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| المؤلفون: | Gabriella Ficz, Wolf Reik, Myriam Hemberger, Ray Kit Ng, Wendy Dean, CF Chan, Cassandra R. Farthing, Simon Andrews |
| المصدر: | PLoS Genetics, Vol 4, Iss 6, p e1000116 (2008) PLoS Genetics |
| بيانات النشر: | Public Library of Science (PLoS), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Homeodomain Proteins - Genetics - Metabolism, Male, Cancer Research, Developmental Biology/Germ Cells, Chromosomal Proteins, Non-Histone, Left-Right Determination Factors, Stem Cells - Physiology, Epigenesis, Genetic, Mice, Transforming Growth Factor beta, Membrane Glycoproteins - Genetics - Metabolism, Nuclear Reprogramming, Developmental Biology/Developmental Molecular Mechanisms, Induced pluripotent stem cell, Promoter Regions, Genetic, RNA-Directed DNA Methylation, Genetics (clinical), Molecular Biology/DNA Methylation, Cells, Cultured, Genetics, Genome, Membrane Glycoproteins, Stem Cells, Transforming Growth Factor Beta - Genetics - Metabolism, Gene Expression Regulation, Developmental, Nanog Homeobox Protein, Cellular Reprogramming, Spermatozoa, Developmental Biology/Stem Cells, Neoplasm Proteins, Chromosomal Proteins, Non-Histone - Genetics - Metabolism, DNA methylation, Female, Reprogramming, Research Article, Homeobox protein NANOG, Pluripotent Stem Cells, lcsh:QH426-470, Epidermal Growth Factor - Genetics - Metabolism, Rex1, Cell Biology/Developmental Molecular Mechanisms, Membrane Proteins - Genetics - Metabolism, Mice, Inbred Strains, Biology, Epigenetics of physical exercise, Neoplasm Proteins - Genetics - Metabolism, Genetics and Genomics/Epigenetics, Animals, Molecular Biology, Cell potency, Ecology, Evolution, Behavior and Systematics, Cell Biology/Gene Expression, Homeodomain Proteins, Epidermal Growth Factor, Membrane Proteins, DNA Methylation, Microarray Analysis, lcsh:Genetics, Pluripotent Stem Cells - Physiology, Developmental Biology/Cell Differentiation, Spermatozoa - Physiology |
| الوصف: | DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, sperm, trophoblast stem (TS) cells, and primary embryonic fibroblasts (pMEFs). Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency genes in the early embryo is thus crucial for transmission of pluripotency. © 2008 Farthing et al. link_to_subscribed_fulltext |
| اللغة: | English |
| تدمد: | 1553-7404 1553-7390 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::527d68282112680943e1cabbf6635dc3Test http://europepmc.org/articles/PMC2432031?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....527d68282112680943e1cabbf6635dc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537404 15537390 |
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