Nascent transcriptome reveals orchestration of zygotic genome activation in early embryogenesis.
Nascent transcriptome reveals orchestration of zygotic genome activation in early embryogenesis.
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DOI：
10.1016/j.cub.2022.07.078
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发表时间：
2022-10-10
期刊：
影响因子：
9.2
通讯作者：
Good, Matthew C.
中科院分区：
文献类型：
--
作者：
Chen, Hui;Good, Matthew C.
早期胚胎发育需要母体向合子的转变，在此期间，转录沉默的细胞核在合子基因组激活(ZGA)过程中开始广泛的基因表达。ZGA对早期细胞的命运和胚层的确定至关重要，ZGA的时机受到多种机制的调节。然而，对于这些机制是否相互关联并在不同物种之间存在差异，以及生殖层特异性基因激活的时间是否在时间上有序，仍存在争议。在一些胚胎模型中，广泛的ZGA起始是时空分级的，但尚不清楚转录组是否遵循这种模式。解决这些问题的一个主要挑战是准确地测量每个基因激活的时间。在这里，我们使用5-乙炔基尿苷(EU)对非洲爪哇胚胎中的新生转录组进行代谢性标记和鉴定。我们发现，Eu-RNA-seq在检测ZGA转录组方面优于总RNA-seq，ZGA转录组以母系合子基因的转录为主，从而改进了ZGA的计时确定。我们发现了单个基因激活的离散时空模式，大多数遵循与细胞大小梯度相关的ZGA的空间模式。我们进一步揭示了转录需要一段时间的发育过程，并且ZGA可以被放线菌亚胺早熟诱导，可能是通过延长间期。最后，大多数外胚层基因比内胚层基因更早被激活，这表明胚层特定基因的时间编排，可能与ZGA的空间分级模式有关。总之，我们的研究为ZGA转录组的组成和动力学、调节ZGA时机的机制以及它在早期细胞命运开始中的作用提供了基本的新见解。通过描绘整个非洲爪哇胚泡和被解剖的亚区合子基因组激活(ZGA)期间的新生转录组，Chen等人。揭示母体受精卵基因的主要转录和不同的空间模式，协调ZGA的调节机制，并发现与生殖层特定基因的顺序激活有关。
Early embryo development requires maternal-to-zygotic transition, during which transcriptionally silent nuclei begin widespread gene expression during zygotic genome activation (ZGA). ZGA is vital for early cell fating and germ layer specification, and ZGA timing is regulated by multiple mechanisms. However, controversies remain about whether these mechanisms are interrelated and vary among species and whether the timing of germ layer-specific gene activation is temporally ordered. In some embryonic models, widespread ZGA onset is spatiotemporally graded, yet it is unclear whether the transcriptome follows this pattern. A major challenge in addressing these questions is to accurately measure the timing of each gene activation. Here, we metabolically label and identify the nascent transcriptome using 5-ethynyl uridine (EU) in Xenopus blastula embryos. We find that EU-RNA-seq outperforms total RNA-seq in detecting the ZGA transcriptome, which is dominated by transcription from maternal-zygotic genes, enabling improved ZGA timing determination. We uncover discrete spatiotemporal patterns for individual gene activation, a majority following a spatial pattern of ZGA that is correlated with a cell-size gradient. We further reveal that transcription necessitates a period of developmental progression and that ZGA can be precociously induced by cycloheximide, potentially through elongation of interphase. Finally, most ectodermal genes are activated earlier than endodermal genes, suggesting a temporal orchestration of germ layer-specific genes, potentially linked to the spatially graded pattern of ZGA. Together, our study provides fundamental new insights into the composition and dynamics of the ZGA transcriptome, mechanisms regulating ZGA timing, and its role in the onset of early cell fating. By profiling the nascent transcriptome during zygotic genome activation (ZGA) from whole Xenopus blastula and dissected subregions, Chen et al. unveil predominant transcription from maternal-zygotic genes and distinct spatial patterns, reconcile regulatory mechanisms of ZGA and discover a link to sequential activation of germ layer-specific genes.
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