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The co-regulation mechanism of transcription factors in the human gene regulatory network.


ABSTRACT: The co-regulation of transcription factors (TFs) has been widely observed in various species. Why is such a co-regulation mechanism needed for transcriptional regulation? To answer this question, the following experiments and analyses were performed. First, examination of the human gene regulatory network (GRN) indicated that co-regulation was significantly enriched in the human GRN. Second, mathematical simulation of an artificial regulatory network showed that the co-regulation mechanism was related to the biphasic dose-response patterns of TFs. Third, the relationship between the co-regulation mechanism and the biphasic dose-response pattern was confirmed using microarray experiments examining different time points and different doses of the toxicant tetrachlorodibenzodioxin. Finally, two mathematical models were constructed to mimic highly co-regulated networks (HCNs) and little co-regulated networks (LCNs), and we found that HCNs were more robust to parameter perturbation than LCNs, whereas LCNs were faster in adaptation to environmental changes than HCNs.

SUBMITTER: Kim J 

PROVIDER: S-EPMC3467061 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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The co-regulation mechanism of transcription factors in the human gene regulatory network.

Kim Junil J   Choi Minsoo M   Kim Jeong-Rae JR   Jin Hua H   Kim V Narry VN   Cho Kwang-Hyun KH  

Nucleic acids research 20120713 18


The co-regulation of transcription factors (TFs) has been widely observed in various species. Why is such a co-regulation mechanism needed for transcriptional regulation? To answer this question, the following experiments and analyses were performed. First, examination of the human gene regulatory network (GRN) indicated that co-regulation was significantly enriched in the human GRN. Second, mathematical simulation of an artificial regulatory network showed that the co-regulation mechanism was r  ...[more]

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