دورية أكاديمية
Losing Dnmt3a dependent methylation in inhibitory neurons impairs neural function by a mechanism impacting Rett syndrome
| العنوان: | Losing Dnmt3a dependent methylation in inhibitory neurons impairs neural function by a mechanism impacting Rett syndrome |
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| المؤلفون: | Laura A Lavery, Kerstin Ure, Ying-Wooi Wan, Chongyuan Luo, Alexander J Trostle, Wei Wang, Haijing Jin, Joanna Lopez, Jacinta Lucero, Mark A Durham, Rosa Castanon, Joseph R Nery, Zhandong Liu, Margaret Goodell, Joseph R Ecker, M Margarita Behrens, Huda Y Zoghbi |
| المصدر: | eLife, Vol 9 (2020) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | non-CpG methylation, Dnmt3a, MeCP2, inhibitory neuron, Rett syndrome, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Methylated cytosine is an effector of epigenetic gene regulation. In the brain, Dnmt3a is the sole ‘writer’ of atypical non-CpG methylation (mCH), and MeCP2 is the only known ‘reader’ for mCH. We asked if MeCP2 is the sole reader for Dnmt3a dependent methylation by comparing mice lacking either protein in GABAergic inhibitory neurons. Loss of either protein causes overlapping and distinct features from the behavioral to molecular level. Loss of Dnmt3a causes global loss of mCH and a subset of mCG sites resulting in more widespread transcriptional alterations and severe neurological dysfunction than MeCP2 loss. These data suggest that MeCP2 is responsible for reading only part of the Dnmt3a dependent methylation in the brain. Importantly, the impact of MeCP2 on genes differentially expressed in both models shows a strong dependence on mCH, but not Dnmt3a dependent mCG, consistent with mCH playing a central role in the pathogenesis of Rett Syndrome. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/52981Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.52981 |
| الوصول الحر: | https://doaj.org/article/b078fc09c47f4ff18e2e3557478a806dTest |
| رقم الانضمام: | edsdoj.b078fc09c47f4ff18e2e3557478a806d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.52981 |