Dynamic modeling of cis-regulatory circuits and gene expression prediction via cross-gene identification.
BACKGROUND
Gene expression programs depend on recognition of cis elements in promoter region of target genes by transcription factors (TFs), but how TFs regulate gene expression via recognition of cis elements is still not clear. To study this issue, we define the cis-regulatory circuit of a gene as a system that consists of its cis elements and the interactions among their recognizing TFs and develop a dynamic model to study the functional architecture and dynamics of the circuit. This is in contrast to traditional approaches where a cis-regulatory circuit is constructed by a mutagenesis or motif-deletion scheme. We estimate the regulatory functions of cis-regulatory circuits using microarray data.


RESULTS
A novel cross-gene identification scheme is proposed to infer how multiple TFs coordinate to regulate gene transcription in the yeast cell cycle and to uncover hidden regulatory functions of a cis-regulatory circuit. Some advantages of this approach over most current methods are that it is based on data obtained from intact cis-regulatory circuits and that a dynamic model can quantitatively characterize the regulatory function of each TF and the interactions among the TFs. Our method may also be applicable to other genes if their expression profiles have been examined for a sufficiently long time.


CONCLUSIONS
In this study, we have developed a dynamic model to reconstruct cis-regulatory circuits and a cross-gene identification scheme to estimate the regulatory functions of the TFs that control the regulation of the genes under study. We have applied this method to cell cycle genes because the available expression profiles for these genes are long enough. Our method not only can quantify the regulatory strengths and synergy of the TFs but also can predict the expression profile of any gene having a subset of the cis elements studied.
Lin
Li-Hsieh
LH
Lab. of System Biology, National Tsing Hua University, Hsinchu, 300, Taiwan. LHlin@moti.ee.nthu.edu.tw
Lee
Hsiao-Ching
HC
Li
Wen-Hsiung
WH
Chen
Bor-Sen
BS
D002453:Cell Cycle / Q000235:genetics*; D019926:Cyclin B / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D008074:Lipoproteins / Q000235:genetics; D008957:Models, Genetic; D005810:Multigene Family; D010675:Pheromones; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology; D015003:Yeasts / Q000166:cytology / Q000235:genetics
C093749:CLB2 protein, S cerevisiae; D019926:Cyclin B; D008074:Lipoproteins; C095063:MFA2 protein, S cerevisiae; D010675:Pheromones; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors