Proximal genomic localization of STAT1 binding and regulated transcriptional activity.
BACKGROUND
Signal transducer and activator of transcription (STAT) proteins are key regulators of gene expression in response to the interferon (IFN) family of anti-viral and anti-microbial cytokines. We have examined the genomic relationship between STAT1 binding and regulated transcription using multiple tiling microarray and chromatin immunoprecipitation microarray (ChIP-chip) experiments from public repositories.


RESULTS
In response to IFN-gamma, STAT1 bound proximally to regions of the genome that exhibit regulated transcriptional activity. This finding was consistent between different tiling microarray platforms, and between different measures of transcriptional activity, including differential binding of RNA polymerase II, and differential mRNA transcription. Re-analysis of tiling microarray data from a recent study of IFN-gamma-induced STAT1 ChIP-chip and mRNA expression revealed that STAT1 binding is tightly associated with localized mRNA transcription in response to IFN-gamma. Close relationships were also apparent between STAT1 binding, STAT2 binding, and mRNA transcription in response to IFN-alpha. Furthermore, we found that sites of STAT1 binding within the Encyclopedia of DNA Elements (ENCODE) region are precisely correlated with sites of either enhanced or diminished binding by the RNA polymerase II complex.


CONCLUSIONS
Together, our results indicate that STAT1 binds proximally to regions of the genome that exhibit regulated transcriptional activity. This finding establishes a generalized basis for the positioning of STAT1 binding sites within the genome, and supports a role for STAT1 in the direct recruitment of the RNA polymerase II complex to the promoters of IFN-gamma-responsive genes.
Wormald
Samuel
S
Division of Bioinformatics, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. wormald@wehi.edu.au
Hilton
Douglas J
DJ
Smyth
Gordon K
GK
Speed
Terence P
TP
D001665:Binding Sites / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050795:STAT2 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*
D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D007371:Interferon-gamma