Inhibition of neddylation disturbs zygotic genome activation through histone modification change and leads to early development arrest in mouse embryos
Publish-translational modification and fine-tuned protein turnover are crucial in mammalian early embryo development. In addition to the classic protein degradation promoting ubiquitination, new types of ubiquitination-like modification are not yet been fully understood. Here, we demonstrate the part and potential mechanisms of 1 ubiquitination-like modification, neddylation, in mouse preimplantation embryo development. Given specific inhibitors, zygotes demonstrated a dramatically decreased cleavage rate and just about all unsuccessful to go in some-cell stage. Transcriptional profiling demonstrated genes were differentially expressed in pathways involving cell fate determination and cell differentiation, including several lower-controlled zygotic genome activation (ZGA) marker genes. A low degree of phosphorylated RNA polymerase II was detected, indicating impaired gene transcription within the embryo cell nucleus. Proteomic data demonstrated that differentially expressed proteins were filled with histone modifications. We confirmed the decreased in methyltransferase (KMT2D) expression and home loan business histone H3K4me3. Simultaneously, acetyltransferase (CBP/p300) reduced, while deacetylase (HDAC6) elevated, leading to an attenuation in histone H3K27ac. Furthermore, we observed the up-regulation in YAP1 and RPL13 activities, indicating potential abnormalities within the downstream response of Hippo signaling path. In conclusion, we discovered that inhibition of neddylation caused epigenetic alterations in early embryos and brought to abnormalities in related downstream signaling pathways. This research sheds light upon new types of ubiquitination controlling mammalian embryonic TAS4464 development and could lead to help analysis of female infertility pathology.