Identifying regulatory targets of cell cycle transcription factors using gene expression and ChIP-chip data.
BACKGROUND
ChIP-chip data, which indicate binding of transcription factors (TFs) to DNA regions in vivo, are widely used to reconstruct transcriptional regulatory networks. However, the binding of a TF to a gene does not necessarily imply regulation. Thus, it is important to develop methods to identify regulatory targets of TFs from ChIP-chip data.


RESULTS
We developed a method, called Temporal Relationship Identification Algorithm (TRIA), which uses gene expression data to identify a TF's regulatory targets among its binding targets inferred from ChIP-chip data. We applied TRIA to yeast cell cycle microarray data and identified many plausible regulatory targets of cell cycle TFs. We validated our predictions by checking the enrichments for functional annotation and known cell cycle genes. Moreover, we showed that TRIA performs better than two published methods (MA-Network and MFA). It is known that co-regulated genes may not be co-expressed. TRIA has the ability to identify subsets of highly co-expressed genes among the regulatory targets of a TF. Different functional roles are found for different subsets, indicating the diverse functions a TF could have. Finally, for a control, we showed that TRIA also performs well for cell-cycle irrelevant TFs.


CONCLUSIONS
Finding the regulatory targets of TFs is important for understanding how cells change their transcription program to adapt to environmental stimuli. Our algorithm TRIA is helpful for achieving this purpose.
Wu
Wei-Sheng
WS
Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan. wessonwu@gmail.com
Li
Wen-Hsiung
WH
Chen
Bor-Sen
BS
D000465:Algorithms; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D018797:Cell Cycle Proteins; D014157:Transcription Factors