Telomeres cooperate in zygotic genome activation by affecting DUX4/Dux transcription.
Telomeres cooperate in zygotic genome activation by affecting DUX4/Dux transcription.
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DOI：
10.1016/j.isci.2023.106158
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发表时间：
2023-03-17
期刊：
影响因子：
5.8
通讯作者：
Leng, Lizhi
中科院分区：
文献类型：
--
作者：
Zhang, Xiaoru;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
一旦基因组染色质状态在新形成的合子中组织起来，合子基因组激活（ZGA）就会启动。端粒是染色体末端的特化染色质结构，在胚胎发生早期被重置，而着床前胚胎端粒变化的细节和意义尚不清楚。我们发现，在人类和小鼠胚胎的小ZGA阶段，端粒长度缩短，在大ZGA阶段，端粒长度明显延长。ZGA先导因子DUX4/Dux的表达与端粒长度呈负相关。ATAC测序数据显示，在人类小ZGA中，DUX4启动子区域（即染色体4q的亚端粒）的染色质可及性峰短暂增加。端粒区异染色质H3K9me3的减少也协同激活了人胚胎干细胞中DUX4与p53的表达。我们在此提出，端粒通过染色质重塑调节DUX4/Dux的表达，从而参与ZGA。在ZGA过程中端粒长度发生重塑，DUX4/Dux的表达与端粒长度呈负相关。H3K9me3通过影响p53结合在DUX4表达中发挥TPE效应
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. 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
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DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
影响因子：
2
作者：
He, Caixia;Jing, Shuang;Zeng, Sicong
通讯作者：
Zeng, Sicong
端粒长度与 ES/iPS 细胞真实多能性的关联
影响因子：
44.1
作者：
Huang, Junjiu;Wang, Fang;Liu, Lin
通讯作者：
Liu, Lin
影响因子：
3.7
作者：
Chagin, Vadim O.;Reinhart, Britta;Cardoso, M. Cristina
通讯作者：
Cardoso, M. Cristina
DOI：
10.1016/j.bbrc.2022.10.093
发表时间：
2022-11-04
影响因子：
3.1
作者：
He, Caixia;Zhang, Xiaorui;Zeng, Sicong
通讯作者：
Zeng, Sicong