L1 retrotransposition is activated by Ten-eleven-translocation protein 1 and repressed by methyl-CpG binding proteins
| العنوان: | L1 retrotransposition is activated by Ten-eleven-translocation protein 1 and repressed by methyl-CpG binding proteins |
|---|---|
| المؤلفون: | Anne Lehmkuhl, Ines Hellmann, Cathia Rausch, Florian D. Hastert, M. Cristina Cardoso, Peng Zhang, Anne K. Ludwig, Heinrich Leonhardt, Martha Smets |
| المصدر: | Nucleus |
| بيانات النشر: | Taylor & Francis, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Methyl-CpG-Binding Protein 2, Retrotransposon, Biology, MECP2, Cell Line, Mixed Function Oxygenases, 03 medical and health sciences, Mice, Rett syndrome, Proto-Oncogene Proteins, Animals, Humans, 5-hydroxymethylcytosine, Psychological repression, Methyl-CpG binding, Original Research, Genetics, DNA methylation, Cell Biology, DNA-binding domain, Methylation, repetitive elements, DNA-Binding Proteins, 030104 developmental biology, DNA Transposable Elements, genome stability, Binding domain |
| الوصف: | One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter. Finally, we demonstrate that the methyl-CpG binding domain, as well as the adjacent non-sequence specific DNA binding domain of Mecp2 are each sufficient to mediate repression of Tet1-induced L1 mobilization. Our study reveals a mechanism how L1 elements get activated in the absence of Mecp2 and suggests that Tet1 may contribute to Mecp2/Mbd2-deficiency phenotypes, such as the Rett syndrome. We propose that the balance between methylation “reader” and “eraser/writer” controls L1 retrotransposition. |
| اللغة: | English |
| تدمد: | 1949-1042 1949-1034 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::62d147daec5c112bed9d5c413dd1b6d9Test http://europepmc.org/articles/PMC5703239Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....62d147daec5c112bed9d5c413dd1b6d9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19491042 19491034 |
|---|