Bioinformatic analysis reveals cRel as a regulator of a subset of interferon-stimulated genes.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Lai WeiLawrence M Pfeffer

Abstract

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 kappaB (NFkappaB) 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.

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Citations

Apr 2, 2010·Journal of Virology·Kristine M RoseSusan R Weiss
Jul 9, 2011·BMC Genomics·Geir K SandveEivind Hovig
Aug 7, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Brenda MarshMary P Stenzel-Poore
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Jun 24, 2017·Biochemical and Biophysical Research Communications·Susan R PfefferLawrence M Pfeffer
Jan 7, 2020·Oncotarget·Sanith CheriyamundathAvri Ben-Ze'ev
Apr 28, 2017·Frontiers in Cellular Neuroscience·Megan B Wood, Jian Zuo

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