Higuchi Chika, Yamamoto Mari, Shin Seung-Wook, Miyamoto Kei, Matsumoto Kazuya
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan.
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biol Open. 2019 Oct 29;8(10):bio048652. doi: 10.1242/bio.048652.
During the maternal-to-zygotic transition (MZT), mRNAs and proteins stored in oocytes are degraded and zygotic genes are activated. We have previously shown that the ubiquitin-proteasome system (UPS)-mediated degradation of maternal proteins plays a role in the onset of zygotic transcription. However, it is still unclear which maternal proteins should be degraded for zygotic genome activation and ensuring subsequent embryonic development. In this study, we screen for these maternal factors that are degraded via the UPS. We thus identified a maternal protein PIASy (protein inhibitor of activated STATy), which is an E3 SUMO ligase. The overexpression of PIASy in fertilized embryos causes developmental arrest at the two-cell stage due to severe abnormal chromosome segregation and impaired zygotic transcription. We find that this developmental role of PIASy is related to its SUMOylation activity. Moreover, PIASy overexpression leads to increased trimethylation of histone H3 lysine 9 (H3K9me3) in two-cell nuclei and enhanced translocation of H3K9me3 methyltransferase to the pronucleus. Hence, PIASy is a maternal factor that is degraded after fertilization and may be important for the proper induction of zygotic genome activation and embryonic development.
在母源-合子转变（MZT）过程中，卵母细胞中储存的mRNA和蛋白质会被降解，合子基因被激活。我们之前已经表明，泛素-蛋白酶体系统（UPS）介导的母源蛋白降解在合子转录起始中发挥作用。然而，对于合子基因组激活以及确保后续胚胎发育而言，究竟哪些母源蛋白应该被降解仍不清楚。在本研究中，我们筛选了通过UPS降解的这些母源因子。因此，我们鉴定出一种母源蛋白PIASy（活化STATy的蛋白抑制剂），它是一种E3 SUMO连接酶。在受精胚胎中过表达PIASy会导致在二细胞阶段发育停滞，原因是严重的染色体分离异常和合子转录受损。我们发现PIASy的这种发育作用与其SUMO化活性有关。此外，PIASy过表达会导致二细胞核中组蛋白H3赖氨酸9（H3K9me3）的三甲基化增加，以及H3K9me3甲基转移酶向原核的易位增强。因此，PIASy是一种受精后被降解的母源因子，可能对于合子基因组激活和胚胎发育的正确诱导很重要。
