Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment
| العنوان: | Telomere dysfunction cooperates with epigenetic alterations to impair murine embryonic stem cell fate commitment |
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| المؤلفون: | Lea Harrington, Tsz Wai Chu, Julissa Tsao, Neil Winegarden, Cheryl H. Arrowsmith, Monika Sharma, Mathieu Lupien, Danielle A Henry, Aditi Qamra, Dalia Barsyte-Lovejoy, Mélanie Criqui |
| المصدر: | eLife, Vol 9 (2020) eLife |
| بيانات النشر: | eLife Sciences Publications, Ltd, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, QH301-705.5, Science, Cellular differentiation, macromolecular substances, Biology, General Biochemistry, Genetics and Molecular Biology, Epigenesis, Genetic, Histones, Mice, 03 medical and health sciences, 0302 clinical medicine, Animals, Telomerase reverse transcriptase, Epigenetics, Biology (General), Cellular Senescence, mouse, epigenetics, General Immunology and Microbiology, General Neuroscience, telomerase reverse transcriptase, General Medicine, Telomere, embryonic stem cells, Chromosomes and Gene Expression, telomeres, Embryonic stem cell, Chromatin, Cell biology, cell differentiation, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, Medicine, Stem cell, PRC2, Research Article |
| الوصف: | The precise relationship between epigenetic alterations and telomere dysfunction is still an extant question. Previously, we showed that eroded telomeres lead to differentiation instability in murine embryonic stem cells (mESCs) via DNA hypomethylation at pluripotency-factor promoters. Here, we uncovered that telomerase reverse transcriptase null (Tert-/-) mESCs exhibit genome-wide alterations in chromatin accessibility and gene expression during differentiation. These changes were accompanied by an increase of H3K27me3 globally, an altered chromatin landscape at the Pou5f1/Oct4 promoter, and a refractory response to differentiation cues. Inhibition of the Polycomb Repressive Complex 2 (PRC2), an H3K27 tri-methyltransferase, exacerbated the impairment in differentiation and pluripotency gene repression in Tert-/- mESCs but not wild-type mESCs, whereas inhibition of H3K27me3 demethylation led to a partial rescue of the Tert-/- phenotype. These data reveal a new interdependent relationship between H3K27me3 and telomere integrity in stem cell lineage commitment that may have implications in aging and cancer. |
| تدمد: | 2050-084X |
| DOI: | 10.7554/elife.47333 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8797a3a70a6df308d56ce4ae2dddc0ae https://doi.org/10.7554/elife.47333 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8797a3a70a6df308d56ce4ae2dddc0ae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2050084X |
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| DOI: | 10.7554/elife.47333 |