The methyltransferase Setdb1 is essential for meiosis and mitosis in mouse oocytes and early embryos

Citations Over TimeTop 10% of 2016 papers

Abstract

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 downregulates rather than silences expression of ERVK and ERVL-MaLR retrotransposons and associated chimearic transcripts during oogenesis. Our results identify Setdb1 as a newly discovered meiotic and embryonic competence factor safeguarding genome integrity at the onset of life.

Related Papers

• → Oogenesis in Xenopus laevis (Daudin). I. Stages of oocyte development in laboratory maintained animals(1972)1,848 cited
• → Role of Bicaudal-D in patterning the Drosophila egg chamber in mid-oogenesis(1996)79 cited
• → Ovary structure and oogenesis in Cirratulus cirratus (Polychaeta: Cirratulidae)(1971)37 cited
• Histological observation on the oogenesis and oocyte apoptosis of atractomorpha sinensis Bolivar(2007)
• [Characteristics of synthesis of mitochondrial proteins during oogenesis in the loach].(1976)