Computationally Identifying Novel NF-κB-Regulated Immune Genes in the Human Genome

Abstract

Identifying novel NF-κB-regulated immune genes in the human genome is important to our understanding of immune mechanisms and immune diseases. We fit logistic regression models to the promoters of 62 known NF-κB-regulated immune genes, to find patterns of transcription factor binding in the promoters of genes with known immune function. Using these patterns, we scanned the promoters of additional genes to find matches to the patterns, selected those with NF-κB binding sites conserved in the mouse or fly, and then confirmed them as NF-κB-regulated immune genes based on expression data. Among 6440 previously identified promoters in the human genome, we found 28 predicted immune gene promoters, 19 of which regulate genes with known function, allowing us to calculate specificity of 93%–100% for the method. We calculated sensitivity of 42% when searching the 62 known immune gene promoters. We found nine novel NF-κB-regulated immune genes which are consistent with available SAGE data. Our method of predicting gene function, based on characteristic patterns of transcription factor binding, evolutionary conservation, and expression studies, would be applicable to finding genes with other functions.

Susceptibility genes for Kawasaki disease: toward implementation of personalized medicine

“…79 Therefore, we speculated that ITPKC plays a significant role in the immune system and is probably related to inflammation. The finding of the predicted nuclear factor-kB binding sequence in the promoter of ITPKC in an in silico study 83 is in accordance with our speculation.…”

Molecular Genetics of Kawasaki Disease

“…Therefore, we speculated that ITPKC might be related to inflammation. Previous in silico study (75), which has predicted NF-kB binding sequence in the promoter of ITPKC, supported the idea that ITPKC is a potent immune gene.…”

Genome-Wide Analysis of Gene Expression in T Cells to Identify Targets of the NF-κB Transcription Factor c-Rel

“…Previously, the number of binding motifs for a particular transcription factor has been successfully used to predict the response to a transcription factor and to predict gene expression patterns during the yeast cell cycle (55). A computational approach to identify NF-B-regulated genes has also shown that, among a group of immune genes, the region immediately upstream of the TSS (ϳ230 bp) contains the highest density of NF-B sites compared with regions further upstream or with the promoters of a random group of genes (56). Thus, a high density of higher affinity NF-B/Rel sites in proximal promoter regions may be an important criterion for the NF-B/Rel dependence of a gene.…”