Li Yongsheng, Shao Tingting, Jiang Chunjie, Bai Jing, Wang Zishan, Zhang Jinwen, Zhang Lili, Zhao Zheng, Xu Juan, Li Xia
College of Bioinformatics Science and Technology and Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University.
Sci Rep. 2015 Nov 3;5:15953. doi: 10.1038/srep15953.
The combinatorial cross-regulation of transcription factors (TFs) plays an important role in cellular identity and function; however, the dynamic regulation of TFs during glioma progression remains largely unknown. Here, we used the genome-wide expression of TFs to construct an extensive human TF network comprising interactions among 513 TFs and to analyse the dynamics of the TF-TF network during glioma progression. We found that the TF regulatory networks share a common architecture and that the topological structures are conserved. Strikingly, despite the conservation of the network architecture, TF regulatory networks are highly grade specific, and TF circuitry motifs are dynamically rewired during glioma progression. In addition, the most frequently observed structure in the grade-specific TF networks was the feedforward loop (FFL). We described applications that show how investigating the behaviour of FFLs in glioblastoma can reveal FFLs (such as RARG-NR1I2-CDX2) that are associated with prognosis. We constructed comprehensive TF-TF networks and systematically analysed the circuitry, dynamics, and topological principles of the networks during glioma progression, which will further enhance our understanding of the functions of TFs in glioma.
转录因子（TFs）的组合交叉调控在细胞特性和功能中起着重要作用；然而，胶质瘤进展过程中转录因子的动态调控仍 largely 未知。在此，我们利用转录因子的全基因组表达构建了一个广泛的人类 TF 网络，该网络包含 513 个转录因子之间的相互作用，并分析了胶质瘤进展过程中 TF-TF 网络的动态变化。我们发现 TF 调控网络具有共同的架构，并且拓扑结构是保守的。令人惊讶的是，尽管网络架构保守，但 TF 调控网络具有高度的分级特异性，并且 TF 电路基序在胶质瘤进展过程中动态重新布线。此外，分级特异性 TF 网络中最常观察到的结构是前馈环（FFL）。我们描述了一些应用，展示了研究胶质母细胞瘤中 FFL 的行为如何揭示与预后相关的 FFL（如 RARG-NR1I2-CDX2）。我们构建了全面的 TF-TF 网络，并系统地分析了胶质瘤进展过程中网络的电路、动态变化和拓扑原理，这将进一步增强我们对转录因子在胶质瘤中功能的理解。
