PMID- 23645984
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130507
LR  - 20220331
IS  - 1177-6250 (Print)
IS  - 1177-6250 (Electronic)
IS  - 1177-6250 (Linking)
VI  - 7
DP  - 2013
TI  - A Comprehensive Profile of ChIP-Seq-Based STAT1 Target Genes Suggests the 
      Complexity of STAT1-Mediated Gene Regulatory Mechanisms.
PG  - 41-56
LID - 10.4137/GRSB.S11433 [doi]
AB  - Interferon-gamma (IFNgamma) 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 IFNgamma 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 
      IFNgamma-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 IFNgamma-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 IFNgamma 
      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 IFNgamma. 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.
FAU - Satoh, Jun-Ichi
AU  - Satoh J
AD  - Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical, 
      University, Noshio, Kiyose, Tokyo, Japan.
FAU - Tabunoki, Hiroko
AU  - Tabunoki H
LA  - eng
PT  - Journal Article
DEP - 20130326
PL  - United States
TA  - Gene Regul Syst Bio
JT  - Gene regulation and systems biology
JID - 101312647
PMC - PMC3623615
OTO - NOTNLM
OT  - ChIP-seq
OT  - GenomeJack
OT  - STAT1
OT  - binding sites
OT  - interferon-gamma
EDAT- 2013/05/07 06:00
MHDA- 2013/05/07 06:01
PMCR- 2013/03/26
CRDT- 2013/05/07 06:00
PHST- 2013/05/07 06:00 [entrez]
PHST- 2013/05/07 06:00 [pubmed]
PHST- 2013/05/07 06:01 [medline]
PHST- 2013/03/26 00:00 [pmc-release]
AID - grsb-7-2013-041 [pii]
AID - 10.4137/GRSB.S11433 [doi]
PST - epublish
SO  - Gene Regul Syst Bio. 2013 Mar 26;7:41-56. doi: 10.4137/GRSB.S11433. Print 2013.