Need Help?


Gene Regulation and Systems Biology

251,101 Journal Article Views | Journal Analytics

A Comprehensive Profile of ChIP-Seq-Based STAT1 Target Genes Suggests the Complexity of STAT1-Mediated Gene Regulatory Mechanisms

Submit a Paper

Publication Date: 26 Mar 2013

Type: Original Research

Journal: Gene Regulation and Systems Biology

Citation: Gene Regulation and Systems Biology 2013:7 41-56

doi: 10.4137/GRSB.S11433


Interferon-gamma (IFNγ) plays a key role in macrophage activation, T helper and regulatory cell differentiation, defense against intracellular pathogens, tissue remodeling, and tumor surveillance. The diverse biological functions of IFN are mediated by direct activation of signal transducer and activator of transcription 1 (STAT1) as well as numerous downstream effector genes. Because a perturbation in STAT1 target gene networks is closely associated with development of autoimmune diseases and cancers, it is important to characterize the global picture of these networks. Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) provides a highly efficient method for genome-wide profiling of DNA-binding proteins. We analyzed the STAT1 ChIP-Seq dataset of IFNγ-stimulated HeLa S3 cells derived from the ENCODE project, along with transcriptome analysis on microarray. We identified 1,441 stringent ChIP-Seq peaks of protein-coding genes. They were located in the promoter (21.5%) and more often in intronic regions (72.2%) with an existence of IFNγ-activated site (GAS) elements. Among the 1,441 STAT1 target genes, 212 genes are known IFN-regulated genes (IRGs) and 194 genes (13.5%) are actually upregulated in response to IFNγ by transcriptome analysis. The panel of upregulated genes constituted IFN-signaling molecular networks pivotal for host defense against infections, where interferon-regulatory factor (IRF) and STAT transcription factors serve as a hub on which biologically important molecular connections concentrate. The genes with the peak location in intronic regions showed significantly lower expression levels in response to IFNγ. These results indicate that the binding of STAT1 to GAS is not sufficient to fully activate target genes, suggesting the high complexity of STAT1-mediated gene regulatory mechanisms.




Supplementary Files 1  (139.05 KB ZIP FORMAT)

BibTex citation   (BIBDESK, LATEX)




What Your Colleagues Say About Gene Regulation and Systems Biology
Publishing in Gene Regulation and Systems Biology was a very positive experience.  I was impressed by the fast and uncomplicated submission process as well as the clear and professional peer review process which helped to improve the manuscript.  The Libertas Academica team was very patient and helpful.  I would definitely recommend the journal to other colleagues in the field!
Dr Cameron Moshfegh (Federal Institute of Technology, Switzerland)
More Testimonials

Quick Links

New article and journal news notification services
Email Alerts RSS Feeds
Facebook Google+ Twitter
Pinterest Tumblr YouTube