受精卵基因组激活 (ZGA)
中文名称
通路描述
受精后，母性和父性原核经历表观遗传修饰的重大变化，包括 DNA 去甲基化和组蛋白甲基化及乙酰化的变化。在小鼠受精卵（可能在人类受精卵中）的 1 细胞阶段，来自女性和雄性基因组的一小波表达发生，这被称为胚胎基因组激活 (EGA)，也称为 ZGA（Asami et al. 2022）。首先转录的位点是双盒转录因子 DUX4 阵列。DUX4 与 ZGA 表达基因（如 ZSCAN4、DUXA、DUXB、LEUTX 和 KDM4E）的启动子结合，并与 Mediator 复合物相互作用以激活转录（Vuoristo et al. 2022）。DUX4 还结合数千个内源性逆转录子（LTR）的长末端重复序列（特别是 HERVL 家族），并激活双向转录，可启动相邻基因的表达（Fu et al. 2019, Low et al. 2021）。有趣的是，这种内源性逆转录病毒的转录似乎在人类胚胎的血浆和组织中产生类似逆转录病毒颗粒的产物（Mondal and Hofschneider 1982）。DUX4 结合 HSATII 着丝粒卫星重复序列（Young et al. 2013, Hendrickson et al. 2017），并启动双向转录（Hendrickson et al. 2017, Shadle et al. 2019）。这些转录产物似乎对于后续形成染色质中心、大型多染色体凝聚体（异染色质）的形成是必需的（Probst et al. 2010）。随后在 2 细胞阶段（小鼠）和 8 细胞阶段（人类）发生主要 ZGA。在主要 ZGA 期间，染色质回归到更常见的构象，基因上的组蛋白 H3 三甲基赖氨酸 -4 的宽区域转换为转录起始位点附近的窄峰（reviewed in Eckersley-Maslin et al. 2018, Schulz and Harrison 2019, Wu and Vastenhouw 2020, Aoki 2022）。此时还添加组蛋白 H3.1 和 H3.2（Ishiuchi et al. 2021）。
英文描述
Zygotic genome activation (ZGA) After fertilization the maternal and paternal pronuclei undergo major changes in epigenetic modifications, including demethylation of DNA and changes in methylation and acetylation of histones. At this 1-cell stage in mouse zygotes and possibly in human zygotes (Asami et al. 2022), a minor wave of expression from both the female and male genomes occurs, the minor zygotic genome activation (ZGA, also known as embryonic genome activation, EGA) (reviewed in Eckersley-Maslin et al. 2018, Schulz and Harrison 2019, Wu and Vastenhouw 2020, Aoki 2022).
Among the first loci to be transcribed is the DUX4 array of double-homeobox transcription factors. (DUX4 appears to be homologous in structure and function with Dux of mice.) DUX4 binds the promoters of ZGA-expressed genes such as ZSCAN4, DUXA, DUXB, LEUTX, and KDM4E and interacts with the Mediator complex to activate transcription (Vuoristo et al. 2022, reviewed in Kobayashi and Tachibana 2021).
DUX4 also binds long terminal repeats (LTRs) of thousands of endogenous retroelements, notably the HERVL family of retroelements, and activates bidirectional transcription that can initiate expression of adjacent genes (reviewed in Fu et al. 2019, Low et al. 2021). Interestingly, this transcription of endogenous retroviruses evidently results in production of retrovirus-like particles in the plasma and tissues of human embryos (Mondal and Hofschneider 1982).
DUX4 binds HSATII pericentric satellite repeats (Young et al. 2013, Hendrickson et al. 2017) and initiates bidirectional transcription (Hendrickson et al. 2017, Shadle et al. 2019). The transcripts appear to be required for subsequent formation of chromocenters, large multichromosome conglomerations of heterochromatin (Probst et al. 2010).
The minor ZGA is followed by the major ZGA at the 2-cell stage in mice and the 8-cell stage in humans. During the major ZGA, chromatin reverts to a more usual configuration, with broad regions of histone H3 trimethyllysine-4 across genes converted to narrow peaks near transcription start sites (reviewed in Eckersley-Maslin et al. 2018, Schulz and Harrison 2019, Wu and Vastenhouw 2020, Aoki 2022). Histones H3.1 and H3.2 are also added at this time (Ishiuchi et al. 2021).
Among the first loci to be transcribed is the DUX4 array of double-homeobox transcription factors. (DUX4 appears to be homologous in structure and function with Dux of mice.) DUX4 binds the promoters of ZGA-expressed genes such as ZSCAN4, DUXA, DUXB, LEUTX, and KDM4E and interacts with the Mediator complex to activate transcription (Vuoristo et al. 2022, reviewed in Kobayashi and Tachibana 2021).
DUX4 also binds long terminal repeats (LTRs) of thousands of endogenous retroelements, notably the HERVL family of retroelements, and activates bidirectional transcription that can initiate expression of adjacent genes (reviewed in Fu et al. 2019, Low et al. 2021). Interestingly, this transcription of endogenous retroviruses evidently results in production of retrovirus-like particles in the plasma and tissues of human embryos (Mondal and Hofschneider 1982).
DUX4 binds HSATII pericentric satellite repeats (Young et al. 2013, Hendrickson et al. 2017) and initiates bidirectional transcription (Hendrickson et al. 2017, Shadle et al. 2019). The transcripts appear to be required for subsequent formation of chromocenters, large multichromosome conglomerations of heterochromatin (Probst et al. 2010).
The minor ZGA is followed by the major ZGA at the 2-cell stage in mice and the 8-cell stage in humans. During the major ZGA, chromatin reverts to a more usual configuration, with broad regions of histone H3 trimethyllysine-4 across genes converted to narrow peaks near transcription start sites (reviewed in Eckersley-Maslin et al. 2018, Schulz and Harrison 2019, Wu and Vastenhouw 2020, Aoki 2022). Histones H3.1 and H3.2 are also added at this time (Ishiuchi et al. 2021).
所含基因
18 个基因