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Nonlinear dynamic trans/cis regulatory circuit for gene transcription via microarray data.

ABSTRACT: The trans-regulatory circuit is considered as the regulatory interactions between upstream regulatory genes and transcription factor binding site motifs or cis elements. And the cis-regulatory circuit is viewed as a dynamic interactive circuit among binding site motifs with their effective action on the expression scheme of target gene. In brief, gene transcription depends on the trans/cis regulatory circuits. In this study, nonlinear trans/cis regulatory circuits for gene transcription in yeast are constructed using microarray data, translation time delay, and information of transcription factors (TFs) binding sites. We provide a useful nonlinear dynamic modeling and develop a parameter estimating method for the construction of trans/cis regulatory circuits, which is powerful for understanding gene transcription. We apply our method to construct trans/cis regulatory circuits of yeast cell cycle-related genes and successfully quantify their regulatory abilities and find possible cis-element interactions. Not only could the data of yeast be applied by our method, but those of other species also could. The proposed method can provide a quantitative basis for system analysis of gene circuits, which is potential for gene regulatory circuit design with a desired gene expression.

SUBMITTER: Chang YH

PROVIDER: S-EPMC2759131 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Nonlinear dynamic trans/cis regulatory circuit for gene transcription via microarray data.

Chang Yu-Hsiang YH Wang Yu-Chao YC Chen Bor-Sen BS

Gene regulation and systems biology 20071012

The trans-regulatory circuit is considered as the regulatory interactions between upstream regulatory genes and transcription factor binding site motifs or cis elements. And the cis-regulatory circuit is viewed as a dynamic interactive circuit among binding site motifs with their effective action on the expression scheme of target gene. In brief, gene transcription depends on the trans/cis regulatory circuits. In this study, nonlinear trans/cis regulatory circuits for gene transcription in yeast ...[more]

PMID: 19936085

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Project description:BackgroundThe cellular signaling pathway (network) is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach.ResultsIn this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network) to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network). Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data.ConclusionWe focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory pathway in Arabidopsis thaliana and metabolic shift pathway from fermentation to respiration in yeast Saccharomyces cerevisiae, are reconstructed using microarray data to evaluate the performance of our proposed method. In the circadian regulatory pathway, we identified mainly the interactions between the biological clock and the photoperiodic genes consistent with the known regulatory mechanisms. We also discovered the now less-known regulations between crytochrome and phytochrome. In the metabolic shift pathway, the casual relationship of enzymatic genes could be detected properly.

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Nonlinear dynamic trans/cis regulatory circuit for gene transcription via microarray data.

Publications

Nonlinear dynamic trans/cis regulatory circuit for gene transcription via microarray data.

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