Zmynd8 Is Essential For Extra-embryonic Vascular Development

Eukaryotic chromatin is composed of nucleosomes that composed of DNA and histone,epigenetic modification can occur on both DNA and histone,thus affect the chromatin structure and transcription factors and other protein bind of DNA,futher activating or inhibiting gene expression and regulating cell behavior.Posttranslational modifications of histones are uaually reversible,through writer and eraser that two oppose enzymes bind or remove modifications at specific sites.There is also a specific class of protein that can recognize modification sites,called reader.Reader interacts with DNA or other proteins through its specific domain.ZMYND8(inc finger MYND(Myeloid,Nervy and DEAF-1)-type containing 8)is a multiple domain reader containing bromodomain,plant homeodomains(PHD)and PWWP domain.Existing studies have confirmed that ZMYND8 is involved in DNA damage response,and works together with other proteins to inhibit gene transcription by damage and promote homologous rcombination repair.Moreover,ZMYND8 as a corepressor involved in tumor suppression in variety of cancers.But the roles of Zmynd8 in development remains unclear,so we mainly explored the roles of Zmynd8 in the development process.Zmynd8 deletion through homologous recombination in mice was found to be fatal in embryonic stage.Futher studies Zmynd8 involve of embryonic development process,found Zmynd8 deletion affect the embryonic vascular development.The blood vessels of the embryo are mainly divided into embryo blood vessels and extraembryonic blood vessels.extra-embryonic blood vessels include yolk sac blood vessels,allantoic blood vessels and placenta blood vessels.In normal mouse embryos,large main blood vessels and multi-layer branching vascular trees were formed on the yolk sac by 9.0 days of embryo,while no large main blood vessels and multi-layer branching vascular trees were formed on the yolk sac of Zmynd8 deficient mouse embryos.Normal embryo allantoic vessel formation,but Zmynd8 deficient mouse embryos allantoic can not form normal tubular structure.Futher found in embryos 9.5 days,normal embryo allantoic and chorionic connection,form the plancental villi,allantoic blood vessel growth into the formation of the placenta layer,Zmynd8 deficient embryos allantoic and chorionic can not connect,not form the placental labyrinth layer.Collect vascular endothelial cells on yolk sac and transcriptomic analysis,the results found some gene involve innate immune response,leukocyte proliferation,nucleotide metabolic process,ribosome biogenesis,myeloid cell differentiation,oxidative phosphorylation process expression change,this maybe Zmynd8 mutation disrupts gene expression profiling of endothelial cells in vascular development.Futher research is needed on how Zmynd8 specifically affects the vascular development of mouse embryos.