Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14850, USA.
Dev Cell. 2021 May 3;56(9):1268-1282.e6. doi: 10.1016/j.devcel.2021.03.024. Epub 2021 Apr 13.
Cell fate commitment is controlled by cis-regulatory elements often located in remote regions of the genome. To examine the role of long-range DNA interactions in early development, we generated a high-resolution contact map of active enhancers in avian neural crest cells. This analysis uncovered a diverse repertoire of enhancers that are part of the gene regulatory network underlying specification. We found that neural crest identity is largely regulated by cis-regulatory elements that propagate signaling inputs to network components. These genomic sensors display a combination of optimal and suboptimal TCF/LEF-binding sites, which allow cells to respond to Wnt signaling in a position-dependent manner. We propose that, rather than acting as upstream activators, signaling systems feed into regulatory circuits in a hub-and-spoke architecture. These results shed light on the tridimensional organization of the neural crest genome and define how signaling systems provide progenitors with spatial cues that transform their molecular identity.
细胞命运的决定受到顺式调控元件的控制，这些元件通常位于基因组的远程区域。为了研究长距离 DNA 相互作用在早期发育中的作用，我们生成了鸟类神经嵴细胞中活性增强子的高分辨率接触图谱。这项分析揭示了一系列多样化的增强子，它们是构成基因调控网络的一部分，是指定的基础。我们发现，神经嵴的身份主要受顺式调控元件的调控，这些元件将信号输入传播到网络组件。这些基因组传感器显示出最佳和次优的 TCF/LEF 结合位点的组合，使细胞能够以位置依赖的方式对 Wnt 信号做出反应。我们提出，信号系统不是作为上游激活剂，而是以轮辐式架构的形式进入调节回路。这些结果揭示了神经嵴基因组的三维组织，并定义了信号系统如何为祖细胞提供空间线索，从而改变它们的分子身份。
