The methyltransferase Setdb1 is essential for meiosis and mitosis in mouse oocytes and early embryos.
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.
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
Angeline
A
Eymery
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
Zichuan
Z
Liu
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland.
Evgeniy A
EA
Ozonov
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland Swiss Institute of Bioinformatics, Basel 4058, Switzerland.
Michael B
MB
Stadler
Friedrich Miescher Institute for Biomedical Research, Basel 4058, Switzerland Faculty of Sciences, University of Basel, Basel 4056, Switzerland antoine.peters@fmi.ch.
Antoine H F M
0000-0002-0311-1887
AH
Peters
D000818:Animals; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D018626:Retroelements / Q000235:genetics / Q000502:physiology
D018626:Retroelements; D011495:Histone-Lysine N-Methyltransferase; C516239:SETDB1 protein, mouse
Histone methylation; Meiosis; Mitosis; Pre-implantation development; Transcriptional regulation