دورية أكاديمية
Targets and genomic constraints of ectopic Dnmt3b expression
| العنوان: | Targets and genomic constraints of ectopic Dnmt3b expression |
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| المؤلفون: | Yingying Zhang, Jocelyn Charlton, Rahul Karnik, Isabel Beerman, Zachary D Smith, Hongcang Gu, Patrick Boyle, Xiaoli Mi, Kendell Clement, Ramona Pop, Andreas Gnirke, Derrick J Rossi, Alexander Meissner |
| المصدر: | eLife, Vol 7 (2018) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2018. |
| سنة النشر: | 2018 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | liver, stem cells, blood, MEFs, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | DNA methylation plays an essential role in mammalian genomes and expression of the responsible enzymes is tightly controlled. Deregulation of the de novo DNA methyltransferase DNMT3B is frequently observed across cancer types, yet little is known about its ectopic genomic targets. Here, we used an inducible transgenic mouse model to delineate rules for abnormal DNMT3B targeting, as well as the constraints of its activity across different cell types. Our results explain the preferential susceptibility of certain CpG islands to aberrant methylation and point to transcriptional state and the associated chromatin landscape as the strongest predictors. Although DNA methylation and H3K27me3 are usually non-overlapping at CpG islands, H3K27me3 can transiently co-occur with DNMT3B-induced DNA methylation. Our genome-wide data combined with ultra-deep locus-specific bisulfite sequencing suggest a distributive activity of ectopically expressed Dnmt3b that leads to discordant CpG island hypermethylation and provides new insights for interpreting the cancer methylome. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/40757; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.40757 |
| URL الوصول: | https://doaj.org/article/ec968c14f5da4542813e3bd8668faa0a |
| رقم الأكسشن: | edsdoj.968c14f5da4542813e3bd8668faa0a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.40757 |