Telomeres cooperate in zygotic genome activation by affecting DUX4 / Dux transcription.

Zygotic genome activation (ZGA) is initiated once the genome chromatin state is organized in the newly formed zygote. Telomeres are specialized chromatin structures at the ends of chromosomes and are reset during early embryogenesis, while the details and significance of telomere changes in preimplantation embryos remain unclear. We demonstrated that the telomere length was shortened in the minor ZGA stage and significantly elongated in the major ZGA stage of human and mouse embryos. Expression of the ZGA pioneer factor was negatively correlated with the telomere length. ATAC sequencing data revealed that the chromatin accessibility peaks on the promoter region (i.e., the subtelomere of chromosome 4q) were transiently augmented in human minor ZGA. Reduction of telomeric heterochromatin H3K9me3 in the telomeric region also synergistically activated expression with p53 in human embryonic stem cells. We propose herein that telomeres regulate the expression of / through chromatin remodeling and are thereby involved in ZGA.