The co-regulation mechanism of transcription factors in the human gene regulatory network.
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.
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
Junil
J
Kim
Minsoo
M
Choi
Jeong-Rae
JR
Kim
Hua
H
Jin
V Narry
VN
Kim
Kwang-Hyun
KH
Cho
D045744:Cell Line, Tumor; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008957:Models, Genetic; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*
D014157:Transcription Factors