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Nuclear reprogramming: the zygotic transcription program is established through an 'erase-and-rebuild' strategy

机译:核重编程:通过“擦除和重建”策略建立合子转录程序

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Oocytes display a maternal-specific gene expression profile, which is switched to a zygotic profile when a haploid set of chromatin is passed on to the fertilized egg that develops into an embryo. The mechanism underlying this transcription reprogramming is currently unknown. Here we demonstrate that by the time when transcription is shut down in germinal vesicle oocytes, a range of general transcription factors and transcriptional regulators are dissociated from the chromatin. The global dissociation of chromatin factors (CFs) disrupts physical contacts between the chromatin and CFs and leads to erasure of the maternal transcription program at the functional level. Critical transcription factors and regulators remain separated from chromatin for a prolonged period, and become re-associated with chromatin shortly after pronuclear formation. This is followed temporally by the re-establishment of nuclear functions such as DNA replication and transcription. We propose that the maternal transcription program is erased during oogenesis to generate a relatively naive chromatin and the zygotic transcription program is rebuilt de novo after fertilization. This process is termed as the "erase-and-rebuild" process, which is used to reset the transcription program, and most likely other nuclear processes as well, from a maternal one to that of the embryo. We further show in the accompanying paper (Gao T, et al., Cell Res 2007; 17:135-150.) that the same strategy is also employed to reprogram transcriptional profiles in somatic cell nuclear transfer and parthenogenesis, suggesting that this model is universally applicable to all forms of transcriptional reprogramming during early embryogenesis. Displacement of CFs from chromatin also offers an explanation for the phenomenon of transcription silence during the maternal to zygotic transition.
机译:卵母细胞显示母源特异性基因表达谱,当单倍体染色质传递到发育成胚胎的受精卵时,卵母细胞会转换为合子谱。目前尚不清楚该转录重编程的基础机制。在这里,我们证明了当发芽囊泡卵母细胞中的转录被关闭时,一系列的一般转录因子和转录调节因子会从染色质上解离。染色质因子(CFs)的整体解离会破坏染色质与CFs之间的物理接触,并导致在功能水平上消除母体转录程序。关键的转录因子和调节剂长时间保持与染色质分离,并在前核形成后不久与染色质重新关联。随后在时间上重新建立核功能,例如DNA复制和转录。我们建议母体转录程序在卵子发生过程中被删除以生成相对幼稚的染色质,并且合子转录程序在受精后从头开始重建。该过程被称为“擦除和重建”过程,用于重置转录程序,以及从母体到胚胎最可能的其他核过程。我们在随附的论文(Gao T等人,Cell Res 2007; 17:135-150。)中进一步表明,相同的策略还用于对体细胞核转移和孤雌生殖中的转录谱进行重新编程,这表明该模型是普遍适用于早期胚胎发生过程中所有形式的转录重编程。 CF从染色质的置换也为母体向合子过渡过程中转录沉默现象提供了解释。

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