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

• Published in: iScience Vol. 26; no. 3; p. 106158
• Main Authors: Zhang, Xiaorui, Zhang, Changquan, Zhou, Di, Zhang, Tianlei, Chen, Xueqin, Ren, Jinlin, He, Caixia, Meng, Fei, Zhou, Qinwei, Yang, Qiaohui, Dai, Congling, Lin, Ge, Zeng, Sicong, Leng, Lizhi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.03.2023; Elsevier
• Subjects: Biological sciences; Genetics; Genomics; Genetics; Genomics; Biological sciences
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.106158

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 DUX4/Dux was negatively correlated with the telomere length. ATAC sequencing data revealed that the chromatin accessibility peaks on the DUX4 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 DUX4 expression with p53 in human embryonic stem cells. We propose herein that telomeres regulate the expression of DUX4/Dux through chromatin remodeling and are thereby involved in ZGA. [Display omitted] •Telomere length undergoes remodeling during the process of ZGA•The expression of DUX4/Dux was negatively correlated with telomere length•H3K9me3 acted as a TPE effector in DUX4 expression by influencing the binding of p53 Biological sciences Genetics Genomics