Identification of putative enhancer-like elements predicts regulatory networks active in planarian adult stem cells
Identification of putative enhancer-like elements predicts regulatory networks active in planarian adult stem cells
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DOI：
10.1101/2022.02.03.479047
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发表时间：
2022-02
期刊：
影响因子：
7.7
通讯作者：
Jakke Neiro;Divya Sridhar;Anish Dattani;A. Aboobaker
中科院分区：
文献类型：
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作者：
Jakke Neiro;Divya Sridhar;Anish Dattani;A. Aboobaker
涡虫已经成为研究再生和干细胞的一个成熟的模型系统，但基因组中的调控元件仍然几乎完全未被描述。在这里，通过整合表观遗传学和表达数据，我们使用多种来源的证据来预测在驱动再生的成体干细胞群体中活跃的增强因子。我们使用ChIP-seq数据来识别与增强子身份和活性一致的组蛋白修饰区域，使用ATAC-seq数据来识别可接近的染色质。重叠这些信号允许识别一组高可信度的候选增强子，预计在涡虫成体干细胞中有活性。这些增强子富含在涡虫成体干细胞中表达的转录因子（TF）和TF家族的预测结合位点。足迹分析提供了进一步的证据，证明这些潜在的TF结合位点在成体干细胞中可能被占据。我们整合了这些分析，为干细胞中转录因子的调节功能建立可测试的假设，包括多能性如何被调节，以及谱系分化程序如何被控制。我们发现我们预测的grn得到了现有TF RNAi/RNA-seq数据集的独立支持，这进一步证明了我们的工作预测了活性增强子调节成体干细胞和再生机制。
Planarians have become an established model system to study regeneration and stem cells, but the regulatory elements in the genome remain almost entirely undescribed. Here, by integrating epigenetic and expression data we use multiple sources of evidence to predict enhancer elements active in the adult stem cell populations that drive regeneration. We have used ChIP-seq data to identify regions with histone modifications consistent with enhancer identity and activity, and ATAC-seq data to identify accessible chromatin. Overlapping these signals allowed for the identification of a set of high confidence candidate enhancers predicted to be active in planarian adult stem cells. These enhancers are enriched for predicted transcription factor (TF) binding sites for TFs and TF families expressed in planarian adult stem cells. Foot-printing analyses provided further evidence that these potential TF binding sites are potentially occupied in adult stem cells. We integrated these analyses to build testable hypotheses for the regulatory function of transcription factors in stem cells, both with respect to how pluripotency might be regulated, and to how lineage differentiation programs are controlled. We found that our predicted GRNs were independently supported by existing TF RNAi/RNA-seq data sets, providing further evidence that our work predicts active enhancers regulating adult stem cells and regenerative mechanisms.