期刊
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
卷 28, 期 9, 页码 541-551出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/jir.2007.0136
关键词
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资金
- UT Center for Genomics and Bioinformatics
- UT Center for Neurobiology of Brain Diseases
- NIH [LM007292-03, CA73753]
- Muirhead Chair Endowment
- UT Center for Information Technology Research
- NATIONAL CANCER INSTITUTE [R01CA133322, R01CA073753] Funding Source: NIH RePORTER
- NATIONAL LIBRARY OF MEDICINE [R01LM007292] Funding Source: NIH RePORTER
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 kappa B (NF kappa B) 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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