Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming.
Hierarchical molecular events driven by oocyte-specific factors lead to rapid and extensive reprogramming.
复制标题
DOI：
10.1016/j.molcel.2014.06.024
复制
发表时间：
2014-08-21
期刊：
影响因子：
16
通讯作者：
Gurdon, John B.
中科院分区：
文献类型：
--
作者：
Jullien, Jerome;Miyamoto, Kei;Pasque, Vincent;Allen, George E.;Bradshaw, Charles R.;Garrett, Nigel J.;Halley-Stott, Richard P.;Kimura, Hiroshi;Ohsumi, Keita;Gurdon, John B.
核移植是体细胞核转录重编程的有效途径，但其机制尚不清楚。在这里，我们确定了一系列的分子事件，导致快速转录重编程的体细胞核移植到非洲爪蟾卵母细胞后。RNA-seq分析表明，卵母细胞的重编程导致转录选择性地向卵母细胞而不是多能类型转换，而不需要新的蛋白质合成。单核水平的时程分析表明，在大多数移植的细胞核中，转录重编程以高度分层的方式诱导。我们证明了体细胞-卵母细胞特异性因子的广泛交换介导了重编程，并导致了移植染色质上强大的卵母细胞RNA聚合酶II结合和磷酸化。此外，卵母细胞特异性接头组蛋白B4的全基因组结合支持其在转录重编程中的作用。因此，我们的研究揭示了体细胞染色质上的卵母细胞特异性因子的快速、丰富和逐步加载是成功重编程的重要决定因素。非洲爪蟾卵母细胞在2天内诱导小鼠细胞核中的卵母细胞转录模式重编程需要从体细胞到卵母细胞转录成分的转换异常大量的卵母细胞衍生的RNA聚合酶II驱动重编程卵母细胞接头组蛋白结合体细胞染色质的模式被揭示Jullien et al.鉴定导致体细胞核移植到爪蟾卵母细胞后快速转录重编程的事件序列。转录被选择性地切换到一个卵母细胞型程序的过程中，涉及逐步加载的卵母细胞特异性因子移植到染色质。
Nuclear transfer to oocytes is an efficient way to transcriptionally reprogram somatic nuclei, but its mechanisms remain unclear. Here, we identify a sequence of molecular events that leads to rapid transcriptional reprogramming of somatic nuclei after transplantation to Xenopus oocytes. RNA-seq analyses reveal that reprogramming by oocytes results in a selective switch in transcription toward an oocyte rather than pluripotent type, without requiring new protein synthesis. Time-course analyses at the single-nucleus level show that transcriptional reprogramming is induced in most transplanted nuclei in a highly hierarchical manner. We demonstrate that an extensive exchange of somatic- for oocyte-specific factors mediates reprogramming and leads to robust oocyte RNA polymerase II binding and phosphorylation on transplanted chromatin. Moreover, genome-wide binding of oocyte-specific linker histone B4 supports its role in transcriptional reprogramming. Thus, our study reveals the rapid, abundant, and stepwise loading of oocyte-specific factors onto somatic chromatin as important determinants for successful reprogramming. Xenopus oocytes induce an oocyte transcription pattern in mouse nuclei in 2 days Reprogramming requires a switch from somatic to oocyte transcriptional components Unusually high amounts of oocyte-derived RNA polymerase II drive reprogramming The pattern of oocyte linker histone binding to somatic chromatin is revealed Jullien et al. identify a sequence of events leading to rapid transcriptional reprogramming of somatic nuclei after their transplantation to Xenopus oocytes. Transcription is switched selectively to an oocyte-type program in a process involving stepwise loading of oocyte-specific factors onto transplanted chromatin.
登录
查看更多内容
DOI：
10.1038/nrg2847
发表时间：
2010-08
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.7
作者：
Gao, SR;Chung, YG;Latham, KE
通讯作者：
Latham, KE
影响因子：
10.5
作者：
Gazdag, Emese;Santenard, Angele;Torres-Padilla, Maria-Elena
通讯作者：
Torres-Padilla, Maria-Elena
影响因子：
3.7
作者：
Custodio, Noelia;Antoniou, Michael;Carmo-Fonseca, Maria
通讯作者：
Carmo-Fonseca, Maria
影响因子：
5.3
作者：
Bellier, S;Dubois, MF;Bensaude, O
通讯作者：
Bensaude, O