The methyltransferase Setdb1 is essential for meiosis and mitosis in mouse oocytes and early embryos
| Autor: | Michael B. Stadler, Zichuan Liu, Evgeniy A. Ozonov, Angeline Eymery, Antoine H.F.M. Peters |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Retroelements Embryonic Development Mitosis Biology Oogenesis Chromosome segregation Mice 03 medical and health sciences Prophase Meiosis Chromosome Segregation Histone methylation Animals Kinetochores Molecular Biology Genetics Kinetochore Histone-Lysine N-Methyltransferase 030104 developmental biology Oocytes Spindle organization Female Developmental Biology |
| Zdroj: | Development (Cambridge England) |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.132746 |
| Popis: | Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes and endogenous retroviral elements (ERVs). To address its role in oogenesis and pre-implantation development, we conditionally deleted Setdb1 in growing oocytes. Loss of Setdb1 expression greatly impaired meiosis. It delayed meiotic resumption, altered the dynamics of chromatin condensation, and impaired kinetochore-spindle interactions, bipolar spindle organization, and chromosome segregation in more mature oocytes. The observed phenotypes related to changes in abundance of specific transcripts in mutant oocytes. Setdb1 maternally deficient embryos arrested during pre-implantation development and showed comparable defects during cell cycle progression and in chromosome segregation. Finally, transcriptional profiling data indicate that Setdb1 down-regulates rather than silences expression of ERVK and ERVL-MaLR retrotransposons and associated chimearic transcripts during oogenesis. Our results identify Setdb1 as a novel meiotic and embryonic competence factor safeguarding genome integrity at the onset of life. |
| Databáze: | OpenAIRE |
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