DataSheet1_In silico characterisation of minor wave genes and LINE-1s transcriptional dynamics at murine zygotic genome activation.CSV

Introduction: In mouse, the zygotic genome activation (ZGA) is coordinated by MERVL elements, a class of LTR retrotransposons. In addition to MERVL, another class of retrotransposons, LINE-1 elements, recently came under the spotlight as key regulators of murine ZGA. In particular, LINE-1 transcripts seem to be required to switch-off the transcriptional program started by MERVL sequences, suggesting an antagonistic interplay between LINE-1 and MERVL pathways.
Methods: To better investigate the activities of LINE-1 and MERVL elements at ZGA, we integrated publicly available transcriptomics (RNA-seq), chromatin accessibility (ATAC-seq) and Pol-II binding (Stacc-seq) datasets and characterised the transcriptional and epigenetic dynamics of such elements during murine ZGA.
Results: We identified two likely distinct transcriptional activities characterising the murine zygotic genome at ZGA onset. On the one hand, our results confirmed that ZGA minor wave genes are preferentially transcribed from MERVL-rich and gene-dense genomic compartments, such as gene clusters. On the other hand, we identified a set of evolutionary young and likely transcriptionally autonomous LINE-1s located in intergenic and gene-poor regions showing, at the same stage, features such as open chromatin and RNA Pol II binding suggesting them to be, at least, poised for transcription.
Discussion: These results suggest that, across evolution, transcription of two different classes of transposable elements, MERVLs and LINE-1s, have likely been confined in genic and intergenic regions respectively in order to maintain and regulate two successive transcriptional programs at ZGA.

引言：在小鼠中，合子基因组激活（zygotic genome activation, ZGA）由MERVL元件——一类长末端重复逆转录转座子（LTR retrotransposons）——协同调控。除MERVL外，另一类逆转录转座子LINE-1元件近期也作为小鼠ZGA的关键调控因子受到广泛关注。尤为关键的是，LINE-1转录本似乎是关闭由MERVL序列启动的转录程序所必需的，这提示LINE-1与MERVL通路之间存在拮抗相互作用。
方法：为了更深入地探究ZGA阶段LINE-1与MERVL元件的活性，我们整合了已公开的转录组学（RNA-seq）、染色质开放性（ATAC-seq）及RNA聚合酶II结合（Stacc-seq）数据集，并对小鼠ZGA过程中这些元件的转录与表观遗传动态特征进行了系统表征。
结果：我们鉴定出两种可能截然不同的转录活性模式，可用于描述ZGA启动阶段的小鼠合子基因组。一方面，本研究结果证实，ZGA微波基因优先在富含MERVL且基因密度较高的基因组区域（如基因簇）中进行转录。另一方面，我们在基因间区及基因匮乏区域鉴定出一组进化上年轻且可能具有转录自主性的LINE-1元件；在同一发育阶段，这些元件展现出开放染色质及RNA聚合酶II结合等特征，提示它们至少已处于转录就绪状态。
讨论：上述结果表明，在演化进程中，MERVL与LINE-1这两类转座元件的转录可能分别被限定在基因区与基因间区，从而维持并调控ZGA阶段的两套相继激活的转录程序。