Past Roadblocks and New Opportunities in Transcription Factor Network Mapping.
Past Roadblocks and New Opportunities in Transcription Factor Network Mapping.
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DOI：
10.1016/j.tig.2016.08.009
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发表时间：
2016-11
影响因子：
11.4
通讯作者：
Brent, Michael R.
中科院分区：
文献类型：
--
作者：
Brent, Michael R.
细胞分化和响应外部信号或条件变化的主要机制之一是改变转录因子 (TF) 的活性水平。这通过细胞的转录因子网络改变了目标基因的转录率，最终有助于重新配置细胞状态。自从微阵列为我们提供了了解全局细胞状态的第一个窗口以来，计算生物学家就热切地解决了神经网络（细胞控制电路的关键部分）的映射问题。然而回想起来，稳态 mRNA 丰度水平并不能很好地替代 TF 活性水平和基因转录率。同样，事实证明，通过染色质免疫沉淀绘制 TF 结合图谱对功能调节的预测能力较差，并且比最初希望的更难以系统地阐明完整的网络。这篇综述解释了这些障碍以及当前基于第二代测序的新实验技术的空前蓬勃发展，这些技术为 TF 网络映射带来了快速进展的希望。
One of the principal mechanisms by which cells differentiate and respond to changes in external signals or conditions is by changing the activity levels of transcription factors (TFs). This changes the transcription rates of target genes via the cell’s TF network, which ultimately contributes to reconfiguring cellular state. Since microarrays provided our first window into global cellular state, computational biologists have eagerly attacked the problem of mapping TF networks, a key part of the cell’s control circuitry. In retrospect, however, steady-state mRNA abundance levels were a poor substitute for TF activity levels and gene transcription rates. Likewise, mapping TF binding through chromatin immunoprecipitation proved less predictive of functional regulation and less amenable to systematic elucidation of complete networks than originally hoped. This review explains these roadblocks and the current, unprecedented blossoming of new experimental techniques built on second generation sequencing, which hold out the promise of rapid progress in TF network mapping.
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