Journal Article

Bioinformatic Analysis Reveals cRel as a Regulator of a Subset of Interferon-Stimulated Genes

Heinrich, Kevin, Homayouni, Ramin, Wei, Lai, Berry, Michael W., Xu, Lijing, Fan, Meiyun, Pfeffer, Lawrence M.

2008

Overview

Interferons (IFNs) are critical to the host innate immune response by inducing the expression of a family of early response genes, denoted as IFN-stimulated genes (ISGs). The role of tyrosine phosphorylation of STAT proteins in the transcription activation of ISGs is well-documented. Recent studies have indicated that other transcription factors (TFs) are likely to play a role in regulating ISG expression. Here, we describe a novel integrative approach that combines gene expression profiling, promoter sequence analysis, and literature mining to screen candidate regulatory factors in the IFN signal transduction pathway. Application of this method identified the nuclear factor κB (NFκB) protein, cRel, as a candidate regulatory factor for a subset of ISGs in mouse embryo fibroblasts. Chromatin immunoprecipitation (ChIP) and real-time PCR assays confirmed that cRel directly binds to the promoters of several ISGs, including Cxcl10, Isg15, Gbp2, Ifit3, and Ifi203, and regulates their expression. Thus, our studies identify cRel as an important TF for ISGs, and validate the approach of using Latent Semantic Indexing (LSI)-based methods to identify regulatory factors from microarray data.

• Publisher: SAGE Publications,Mary Ann Liebert, Inc
• Subject: Animals / Cell Line / Chromatin Immunoprecipitation / Computational Biology / DNA binding proteins / Fibroblasts - drug effects / Fibroblasts - immunology / Gene expression / Gene Expression Profiling / Gene Expression Regulation - immunology / Genetic aspects / Health aspects / Interferon / Interferons - immunology / Interferons - pharmacology / Mice / Mice, Inbred C57BL / Physiological aspects / Promoter Regions, Genetic / Proto-Oncogene Proteins c-rel - metabolism / Research Reports / Transcription Factor RelA - metabolism