Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Highly Accessed Open Badges Methodology article

Systematic identification of cell cycle regulated transcription factors from microarray time series data

Chao Cheng1 and Lei M Li12*

Author Affiliations

1 Molecular and Computational biology program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA

2 Department of Mathematics, University of Southern California, Los Angeles, CA 90089, USA

For all author emails, please log on.

BMC Genomics 2008, 9:116  doi:10.1186/1471-2164-9-116

Published: 3 March 2008



The cell cycle has long been an important model to study the genome-wide transcriptional regulation. Although several methods have been introduced to identify cell cycle regulated genes from microarray data, they can not be directly used to investigate cell cycle regulated transcription factors (CCRTFs), because for many transcription factors (TFs) it is their activities instead of expressions that are periodically regulated across the cell cycle. To overcome this problem, it is useful to infer TF activities across the cell cycle by integrating microarray expression data with ChIP-chip data, and then examine the periodicity of the inferred activities. For most species, however, large-scale ChIP-chip data are still not available.


We propose a two-step method to identify the CCRTFs by integrating microarray cell cycle data with ChIP-chip data or motif discovery data. In S. cerevisiae, we identify 42 CCRTFs, among which 23 have been verified experimentally. The cell cycle related behaviors (e.g. at which cell cycle phase a TF achieves the highest activity) predicted by our method are consistent with the well established knowledge about them. We also find that the periodical activity fluctuation of some TFs can be perturbed by the cell synchronization treatment. Moreover, by integrating expression data with in-silico motif discovery data, we identify 8 cell cycle associated regulatory motifs, among which 7 are binding sites for well-known cell cycle related TFs.


Our method is effective to identify CCRTFs by integrating microarray cell cycle data with TF-gene binding information. In S. cerevisiae, the TF-gene binding information is provided by the systematic ChIP-chip experiments. In other species where systematic ChIP-chip data is not available, in-silico motif discovery and analysis provide us with an alternative method. Therefore, our method is ready to be implemented to the microarray cell cycle data sets from different species. The C++ program for AC score calculation is available for download from URL webcite.