Statistical analysis of dynamic transcriptional regulatory network structure.

Here, we present a detailed method for generating a dynamic transcriptional regulatory network from large-scale chromatin immunoprecipitation data, and functional analysis of participating factors through the identification and characterization of significantly overrepresented multi-input motifs in the network. This is done by visualizing interactive data using a network analysis tool, such as Cytoscape, clustering DNA targets of the transcription factors based on their network topologies, and statistically analyzing each cluster based on its size and properties of its members. These analyses yield testable predictions about the conditional and cooperative functions of the factors. This is a versatile approach that allows the visualization of network architecture on a genome-wide level and is applicable to understanding combinatorial control mechanisms of DNA-binding regulators that conditionally cooperate in a wide variety of biological models.

[1]  S. Shen-Orr,et al.  Network motifs in the transcriptional regulation network of Escherichia coli , 2002, Nature Genetics.

[2]  Hanspeter Rottensteiner,et al.  The biochemistry of oleate induction: transcriptional upregulation and peroxisome proliferation. , 2006, Biochimica et biophysica acta.

[3]  Ting Wang,et al.  An improved map of conserved regulatory sites for Saccharomyces cerevisiae , 2006, BMC Bioinformatics.

[4]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[5]  M. G. Koerkamp,et al.  Dissection of transient oxidative stress response in Saccharomyces cerevisiae by using DNA microarrays. , 2002, Molecular biology of the cell.

[6]  M. Gerstein,et al.  The Transcriptional Landscape of the Yeast Genome Defined by RNA Sequencing , 2008, Science.

[7]  Stephen A Ramsey,et al.  Transcriptional Responses to Fatty Acid Are Coordinated by Combinatorial Control , 2022 .

[8]  P. Park ChIP–seq: advantages and challenges of a maturing technology , 2009, Nature Reviews Genetics.

[9]  Trey Ideker,et al.  Transcriptome profiling to identify genes involved in peroxisome assembly and function , 2002, The Journal of cell biology.

[10]  M. Gerstein,et al.  Genomic analysis of regulatory network dynamics reveals large topological changes , 2004, Nature.

[11]  R. Kreisberg,et al.  Environment-responsive transcription factors bind subtelomeric elements and regulate gene silencing , 2011, Molecular systems biology.

[12]  L. Steinmetz,et al.  Bidirectional promoters generate pervasive transcription in yeast , 2009, Nature.

[13]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.