P-276 Telomeres cooperate in zygotic genome activation by affecting DUX4/Dux transcription

Abstract Study question Whether the activation of DUX4, a key inducer in process zygotic genome (ZGA), is associated with telomere length. Summary answer Telomeres regulate expression DUX4/Dux through chromatin remodeling and are thereby involved ZGA. What known already In human early embryos, DUX4 activated as initial stage ZGA, it, turn, activates hundreds genes cleavage-stage embryo. Human localized to subtelomeric region 4q35.2 D4Z4 repeat approximately 10 100 units that encodes homeodomain transcription factor. inversely proportional length myoblasts/myotubes derived from FSHD patients design, size, duration We characterize dynamics telomeres during preimplantation development, assessed relationship between embryos embryonic stem cells. Participants/materials, setting, methods All sperm immature oocytes were collected after obtaining written informed consent donor couples. Telomere gametes by telomere-specific quantitative fluorescence situ hybridization (Q-FISH). Main results role chance Zygotic (ZGA) initiated once state organized newly formed zygote. While specialized structures at ends chromosomes reset embryogenesis, details significance changes remain unclear. demonstrated was shortened minor ZGA significantly elongated major mouse embryos. Expression pioneer factor negatively correlated ATAC-sequencing suggested accessibility peaks on promoter (i.e., subtelomere chromosome 4q) transiently augmented Reduction telomeric heterochromatin H3K9me3 also synergistically p53 hESCs. propose herein Limitations, reasons for caution Since Dux gene not located end chromosome, classical position effect (TPE) pathway may involve its 3D analysis presented Hi-C be able make greater breakthrough confirming relationship. Wider implications findings provided detailed data explored possibility TPE affects regulation suggest process. Trial registration number applicable