Dynamic modeling of cis-regulatory circuits and gene expression prediction via cross-gene identification

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.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.Cis-regulatory circuits have been applied to model cell cycle control and other developmental processes [1,2]. Recently, the genetic regulatory and transcriptional networks of yeast have been studied [3-8]. However, in order to understand the regulation of any particular gene in the network, one should study carefully how the genes in the network collectively operate with remarkable precision in response to environmental cues and the structure and function of the cis-regulatory circuit of the gene [7]. The cis-regulatory circuit of a gene consists of its cis elements, i.e., binding motifs of transcription factor (TF), and the interactions among their recognizing TFs. The cis elements of a gene can be considered as the information processing units in the regulatory circuit; they receive multiple inputs from the TFs that bind the cis elements of the gen