Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse

• DOI: 10.1371/journal.pgen.1005970
• Publication Date: 2016-04-12T17:43:50Z
• Authors: Jeesun Kim; Hongbo Zhao; Jiameng Dan; Soojin Kim; Swanand Hardikar; Debra Hollowell; Kevin Lin; Yue Lu; Yoko Takata; Jianjun Shen; Taiping Chen
• Keywords: Germinal vesicle; Histone H4; Meiosis II

Oocyte meiotic progression and maternal-to-zygote transition are accompanied by dynamic epigenetic changes. The functional significance of these changes the key regulators involved largely unknown. Here we show that Setdb1, a lysine methyltransferase, controls global level histone H3 9 di-methyl (H3K9me2) mark in growing oocytes. Conditional deletion Setdb1 developing oocytes leads to arrest at germinal vesicle meiosis I stages, resulting substantially fewer mature eggs. Embryos derived from eggs exhibit severe defects cell cycle progression, progressive delays preimplantation development, degeneration before reaching blastocyst stage. Rescue experiments expressing wild-type or inactive Setdb1-deficient suggest catalytic activity is essential for early embryogenesis. Mechanistically, up-regulation Cdc14b, dual-specificity phosphatase inhibits greatly contributes phenotype. deficiency also derepression transposons increased DNA damage oocytes, which likely contribute defects. Thus, maternal-effect gene Our results uncover an important link between machinery major signaling pathway governing progression.