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

Junil Kim, Minsoo Choi, Jeong Rae Kim, Hua Jin, V. Narry Kim, Kwang Hyun Cho

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish
Pages (from-to)8849-8861
Number of pages13
JournalNucleic Acids Research
Issue number18
StatePublished - Oct 2012


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