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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)541-551
Number of pages11
JournalJournal of Interferon and Cytokine Research
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2008

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Computational Biology
Interferons
Genes
Transcription Factors
Interferon Regulatory Factors
Chromatin Immunoprecipitation
Gene Expression Profiling
Semantics
Innate Immunity
Transcriptional Activation
Sequence Analysis
Tyrosine
Real-Time Polymerase Chain Reaction
Signal Transduction
Proteins
Embryonic Structures
Fibroblasts
Phosphorylation
Gene Expression

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology
  • Virology

Cite this

Bioinformatic analysis reveals crel as a regulator of a subset of interferon-stimulated genes. / Wei, Lai; Fan, Meiyun; Xu, Lijing; Heinrich, Kevin; Berry, Michael W.; Homayouni, Ramin; Pfeffer, Lawrence.

In: Journal of Interferon and Cytokine Research, Vol. 28, No. 9, 01.09.2008, p. 541-551.

Research output: Contribution to journalArticle

Wei, Lai ; Fan, Meiyun ; Xu, Lijing ; Heinrich, Kevin ; Berry, Michael W. ; Homayouni, Ramin ; Pfeffer, Lawrence. / Bioinformatic analysis reveals crel as a regulator of a subset of interferon-stimulated genes. In: Journal of Interferon and Cytokine Research. 2008 ; Vol. 28, No. 9. pp. 541-551.
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