Telomeres cooperate in zygotic genome activation by affecting DUX4/Dux transcription
Xiaorui Zhang,
Changquan Zhang,
Di Zhou,
Tianlei Zhang,
Xueqin Chen,
Jinlin Ren,
Caixia He,
Fei Meng,
Qinwei Zhou,
Qiaohui Yang,
Congling Dai,
Ge Lin,
Sicong Zeng,
Lizhi Leng
Affiliations
Xiaorui Zhang
Hospital of Hunan Guangxiu, Hunan Normal University, Hunan 410001, China; Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, China; Department of Reproductive Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
Changquan Zhang
NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Di Zhou
NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, China
Tianlei Zhang
Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China
Xueqin Chen
NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Jinlin Ren
Hospital of Hunan Guangxiu, Hunan Normal University, Hunan 410001, China
Caixia He
NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, China
Fei Meng
Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China
Qinwei Zhou
Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China
Qiaohui Yang
NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Congling Dai
Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China; NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China
Ge Lin
Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China; NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, China; Corresponding author
Sicong Zeng
Hospital of Hunan Guangxiu, Hunan Normal University, Hunan 410001, China; Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China; Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, China; Corresponding author
Lizhi Leng
Reproductive and Genetic Hospital of Citic-Xiangya, Hunan 410008, China; NHC Key Laboratory of Human Stem and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, China; Hunan International Scientific and Technological Cooperation Base of Development and Carcinogenesis, Changsha, China; Corresponding author
Summary: 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.
