Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):5862-5869. doi: 10.1073/pnas.1610616114.
Gene regulatory networks (GRNs) provide a transformation function between the static genomic sequence and the primary spatial specification processes operating development. The regulatory information encompassed in developmental GRNs thus goes far beyond the control of individual genes. We here address regulatory information at different levels of network organization, from single node to subcircuit to large-scale GRNs and discuss how regulatory design features such as network architecture, hierarchical organization, and -regulatory logic contribute to the developmental function of network circuits. Using specific subcircuits from the sea urchin endomesoderm GRN, for which both circuit design and biological function have been described, we evaluate by Boolean modeling and in silico perturbations the import of given circuit features on developmental function. The examples include subcircuits encoding positive feedback, mutual repression, and coherent feedforward, as well as signaling interaction circuitry. Within the hierarchy of the endomesoderm GRN, these subcircuits are organized in an intertwined and overlapping manner. Thus, we begin to see how regulatory information encoded at individual nodes is integrated at all levels of network organization to control developmental process.
基因调控网络（GRNs）提供了静态基因组序列和在发育过程中起主要空间规范作用的基因之间的转换功能。因此，发育基因调控网络中包含的调控信息远远超出了单个基因的控制范围。我们在这里讨论了不同层次的网络组织的调控信息，从单个节点到子电路到大规模 GRN，并讨论了网络架构、层次组织和调控逻辑等调控设计特征如何有助于网络电路的发育功能。我们使用海胆内胚层基因调控网络中的特定子电路，这些子电路的电路设计和生物学功能都已被描述，通过布尔建模和计算机模拟干扰来评估特定电路特征对发育功能的重要性。这些例子包括编码正反馈、相互抑制和相干前馈的子电路，以及信号交互电路。在内胚层基因调控网络的层次结构中，这些子电路以交织和重叠的方式组织在一起。因此，我们开始看到在单个节点编码的调控信息如何在网络组织的所有层次上进行整合，以控制发育过程。
