Interacting models of cooperative gene regulation

Das, D., Banerjee, N., Zhang, M. Q. (November 2004) Interacting models of cooperative gene regulation. Proc Natl Acad Sci U S A, 101 (46). pp. 16234-9. ISSN 0027-8424 (Print)

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DOI: 10.1073/pnas.0407365101


Cooperativity between transcription factors is critical to gene regulation. Current computational methods do not take adequate account of this salient aspect. To address this issue, we present a computational method based on multivariate adaptive regression splines to correlate the occurrences of transcription factor binding motifs in the promoter DNA and their interactions to the logarithm of the ratio of gene expression levels. This allows us to discover both the individual motifs and synergistic pairs of motifs that are most likely to be functional, and enumerate their relative contributions at any arbitrary time point for which mRNA expression data are available. We present results of simulations and focus specifically on the yeast cell-cycle data. Inclusion of synergistic interactions can increase the prediction accuracy over linear regression to as much as 1.5- to 3.5-fold. Significant motifs and combinations of motifs are appropriately predicted at each stage of the cell cycle. We believe our multivariate adaptive regression splines-based approach will become more significant when applied to higher eukaryotes, especially mammals, where cooperative control of gene regulation is absolutely essential.

Item Type: Paper
Uncontrolled Keywords: Cell Cycle genetics DNA, Fungal genetics metabolism Databases Genetic Gene Expression Regulation Gene Expression Regulation, Fungal Models Genetic Models Statistical Multivariate Analysis Promoter Regions (Genetics) RNA Fungal genetics RNA Messenger genetics Saccharomyces cerevisiae cytology genetics metabolism Saccharomyces cerevisiae Proteins metabolism Transcription Factors metabolism
Subjects: bioinformatics > computational biology
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL labs > Zhang lab
Depositing User: CSHL Librarian
Date: 16 November 2004
Date Deposited: 09 Feb 2012 16:36
Last Modified: 09 Nov 2017 17:04
PMCID: PMC528978
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