Differential transcript isoform usage pre- and post-zygotic genome activation in zebrafish.

Differential transcript isoform usage pre- and post-zygotic genome activation in zebrafish.
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DOI:
10.1186/1471-2164-14-331
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发表时间:
2013-05-15
期刊:
影响因子:
4.4
通讯作者:
Alestrom P
Alestrom P
中科院分区:
生物学2区
文献类型:
--
作者:
Aanes H;Østrup O;Andersen IS;Moen LF;Mathavan S;Collas P;Alestrom P

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斑马鱼胚胎转录沉默,直到第 10 个细胞周期期间合子基因组激活。转录开始后是涉及细胞物种形成和原肠胚形成的细胞和形态学变化。之前对转录变化的全基因组调查仅评估了基因表达水平;然而,最近的研究表明有必要绘制异构体特异性转录变化图谱。在这里,我们对斑马鱼合子基因组激活(ZGA)前后的转录组序列进行异构体发现和定量。我们在 ZGA 期间鉴定了与细胞粘附、多能性和 DNA 甲基化相关的基因的新同种型和同种型转换。同工型转换事件包括选择性剪接以及转录起始位点和 3' 非翻译区域的变化。即使是 pou5f1、sall4 和 dnmt1 等已充分表征的基因,也能鉴定出新的亚型。参与细胞间相互作用的基因(例如 f11r 和 magi1)显示出具有编码序列改变的异构体开关。我们还检测到超过 1000 个转录本,与母本转录本对应物相比,在受精卵转录时获得更长的 3' 末端外显子。映射到跳跃外显子事件的 ChIP 测序数据揭示了组蛋白 H3K36 三甲基化峰与跳跃外显子之间的相关性,表明表观遗传标记是选择性剪接调控的一部分。这里报道的新亚型和亚型开关包括 ZGA 周围发生的转录、细胞和形态变化的调节因子。我们的数据显示了一系列与亚型相关的功能变化,并代表了对现有早期胚胎转录组的宝贵资源的补充。
Zebrafish embryos are transcriptionally silent until activation of the zygotic genome during the 10th cell cycle. Onset of transcription is followed by cellular and morphological changes involving cell speciation and gastrulation. Previous genome-wide surveys of transcriptional changes only assessed gene expression levels; however, recent studies have shown the necessity to map isoform-specific transcriptional changes. Here, we perform isoform discovery and quantification on transcriptome sequences from before and after zebrafish zygotic genome activation (ZGA). We identify novel isoforms and isoform switches during ZGA for genes related to cell adhesion, pluripotency and DNA methylation. Isoform switching events include alternative splicing and changes in transcriptional start sites and in 3’ untranslated regions. New isoforms are identified even for well-characterized genes such as pou5f1, sall4 and dnmt1. Genes involved in cell-cell interactions such as f11r and magi1 display isoform switches with alterations of coding sequences. We also detect over 1000 transcripts that acquire a longer 3’ terminal exon when transcribed by the zygote compared to their maternal transcript counterparts. ChIP-sequencing data mapped onto skipped exon events reveal a correlation between histone H3K36 trimethylation peaks and skipped exons, suggesting epigenetic marks being part of alternative splicing regulation. The novel isoforms and isoform switches reported here include regulators of transcriptional, cellular and morphological changes taking place around ZGA. Our data display an array of isoform-related functional changes and represent a valuable resource complementary to existing early embryo transcriptomes.
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