文章基本信息

标题：How Retroactivity Affects the Behavior of Incoherent Feedforward Loops
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作者：Junmin Wang ; Calin Belta ; Samuel A. Isaacson 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：12
页码：1-56
DOI：10.1016/j.isci.2020.101779
语种：English
出版社：Elsevier
摘要：SummaryAn incoherent feedforward loop (IFFL) is a network motif known for its ability to accelerate responses and generate pulses. It remains an open question to understand the behavior of IFFLs in contexts with high levels of retroactivity, where an upstream transcription factor binds to numerous downstream binding sites. Here we study the behavior of IFFLs by simulating and comparing ODE models with different levels of retroactivity. We find that increasing retroactivity in an IFFL can increase, decrease, or keep the network's response time and pulse amplitude constant. This suggests that increasing retroactivity, traditionally considered an impediment to designing robust synthetic systems, could be exploited to improve the performance of IFFLs. In contrast, we find that increasing retroactivity in a negative autoregulated circuit can only slow the response. The ability of an IFFL to flexibly handle retroactivity may have contributed to its significant abundance in both bacterial and eukaryotic regulatory networks.Graphical AbstractDisplay OmittedHighlights•Study of how retroactivity affects behaviors of incoherent feedforward loops (IFFLs)•Increasing retroactivity in IFFLs can speed up or slow down the response•Increasing retroactivity in negative autoregulatory loops only slows the response•Tuning retroactivity could be used to improve the performance of synthetic IFFLsBiochemistry; Mathematical Biosciences; Systems Biology