Exploratory bioinformatics investigation reveals importance of "junk" DNA in early embryo development.
Exploratory bioinformatics investigation reveals importance of "junk" DNA in early embryo development.
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DOI：
10.1186/s12864-017-3566-0
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发表时间：
2017-02-23
期刊：
影响因子：
4.4
通讯作者：
Ge SX
中科院分区：
文献类型：
--
作者：
Ge SX
探索性数据分析（EDA）的目标不是测试预先定义的假设，而是找到数据可以告诉我们什么。根据这一策略，我们重新分析了大量的基因组数据，以研究小鼠植入前发育（PD）中复杂的基因调控。从由259个来自受精卵到囊胚阶段的小鼠胚胎细胞组成的单细胞RNA-seq数据集开始，我们重建了PD期间的时间和空间基因表达模式。基因表达的动力学可以部分地解释为转座元件在基因启动子中的富集以及与相应转座子的表达谱的相似性。长末端重复序列（LTR）与2-4细胞阶段的许多邻近基因的短暂、强烈诱导相关，可能是通过为Obox和其他同源框因子提供结合位点。B1和B2西内斯（短散布核元件）与合子基因组激活期间数千个邻近基因的上调相关。这种增强子样效应也见于人Alu和牛tRNA西内斯。西内斯似乎也可以预测胚胎干细胞（ESCs）中的基因表达，从而提高了它们也可能参与调节多能性的可能性。我们还确定了许多潜在的转录因子PD和讨论转座子在增强遗传多样性，特别是对于物种的进化需要较长的世代时间。 连同其他最近的研究，我们的结果提供了进一步的证据，许多转座因子可能在建立早期胚胎的表达景观中发挥作用。它还表明，探索性生物信息学研究可以为进一步研究确定发展途径，并作为从大基因组数据中产生新见解的策略。本文的在线版本（doi：10.1186/s12864-017-3566-0）包含补充材料，可供授权用户使用。
Instead of testing predefined hypotheses, the goal of exploratory data analysis (EDA) is to find what data can tell us. Following this strategy, we re-analyzed a large body of genomic data to study the complex gene regulation in mouse pre-implantation development (PD). Starting with a single-cell RNA-seq dataset consisting of 259 mouse embryonic cells derived from zygote to blastocyst stages, we reconstructed the temporal and spatial gene expression pattern during PD. The dynamics of gene expression can be partially explained by the enrichment of transposable elements in gene promoters and the similarity of expression profiles with those of corresponding transposons. Long Terminal Repeats (LTRs) are associated with transient, strong induction of many nearby genes at the 2-4 cell stages, probably by providing binding sites for Obox and other homeobox factors. B1 and B2 SINEs (Short Interspersed Nuclear Elements) are correlated with the upregulation of thousands of nearby genes during zygotic genome activation. Such enhancer-like effects are also found for human Alu and bovine tRNA SINEs. SINEs also seem to be predictive of gene expression in embryonic stem cells (ESCs), raising the possibility that they may also be involved in regulating pluripotency. We also identified many potential transcription factors underlying PD and discussed the evolutionary necessity of transposons in enhancing genetic diversity, especially for species with longer generation time. Together with other recent studies, our results provide further evidence that many transposable elements may play a role in establishing the expression landscape in early embryos. It also demonstrates that exploratory bioinformatics investigation can pinpoint developmental pathways for further study, and serve as a strategy to generate novel insights from big genomic data. The online version of this article (doi:10.1186/s12864-017-3566-0) contains supplementary material, which is available to authorized users.
影响因子：
12.3
作者：
Urrutia AO;Ocaña LB;Hurst LD
通讯作者：
Hurst LD