Modulation of Gene Expression Regulated by the Transcription Factor NF-κB/RelA

Abstract

Background:Interacting proteins modulate the activity of NF-B/RelA transcription factor and expression of its targets. Results: By analyzing gene expression, protein binding, and DNA binding, we inferred and characterized 8349 such modulations. Conclusion: Different modulator groups affect separate pathways. Significance: We provide new insight into the activity of NF-B/RelA. Our inference model can be applied to other processes and pathways.

Systematic Determination of Human Cyclin Dependent Kinase (CDK)-9 Interactome Identifies Novel Functions in RNA Splicing Mediated by the DEAD Box (DDX)-5/17 RNA Helicases*

“…Proteins physically interacting with transcription factors can alter their mode of action, often on a target-specific manner. To further characterize the potential functional involvement of the CDK9 binding proteins as modulators in gene expression and regulation, we inferred the targets genes of CDK9 with different interacting proteins and their respective modes of regulation using our probabilistic approach (32). For this purpose, the inference considers the effects of the CDK9 interacting proteins as CDK9 "modulators," identifies Table I).…”

“…Genome-wide prediction of the CDK9 modulatory network-Possible biological effects of CDK9 transcriptional complexes were characterized by a probabilistic method recently developed by us for inferring genome-wide modulator-transcription factor (CDK9)-target gene sets, or "triplets" (32,33). In this analysis, all the potential significant triplets were calculated based on a compendium of transcriptional expression profiles of 534 CDK9 interactors identified, CDK9 itself, and predicted CDK9 regulated genes.…”

“…In this analysis, all the potential significant triplets were calculated based on a compendium of transcriptional expression profiles of 534 CDK9 interactors identified, CDK9 itself, and predicted CDK9 regulated genes. We used a compendium of 2158 microarray expression profiles from expO (expression for Oncology) for these calculations (32). Five hundred and thirty-four CDK9 binding proteins mapped into 516 unique genes were used as modulators and 13,162 genes in the Affymetrix HG-U133 plus 2 array were used as target gene candidates in the prediction.…”

“…The three-gene interactions pointing to coregulation, or modulation of CDK9 activity were derived from the analysis of the estimated conditional probabilities of high (or low) expression of the affected target (TG) given a concentration of CDK9 (F) and the gene coding for the interacting protein (M), see equations 1-5 below and (32,33).…”

“…The 2158 conditions in the expO data set were rank-ordered according to the transcript concentrations (at the probeset level) and discretized into three equal bins to identify the high and low expression conditions for each triplet (32). The three-gene interactions pointing to coregulation, or modulation of CDK9 activity were derived from the analysis of the estimated conditional probabilities of high (or low) expression of the affected target (TG) given a concentration of CDK9 (F) and the gene coding for the interacting protein (M), see equations 1-5 below and (32,33).…”