Back to Search
Start Over
The Sin3a repressor complex is a master regulator of STAT transcriptional activity
- Publication Year :
- 2012
- Publisher :
- National Academy of Sciences, 2012.
-
Abstract
- Tyrosine phosphorylation is a hallmark for activation of STAT proteins, but their transcriptional activity also depends on other secondary modifications. Type I IFNs can activate both the ISGF3 (STAT1:STAT2:IRF9) complex and STAT3, but with cell-specific, selective triggering of only the ISGF3 transcriptional program. Following a genome-wide RNAi screen, we identified the SIN3 transcription regulator homolog A (Sin3a) as an important mediator of this STAT3-targeted transcriptional repression. Sin3a directly interacts with STAT3 and promotes its deacetylation. SIN3A silencing results in a prolonged nuclear retention of activated STAT3 and enhances its recruitment to the SOCS3 promoter, concomitant with histone hyperacetylation and enhanced STAT3-dependent transcription. Conversely, Sin3a is required for ISGF3-dependent gene transcription and for an efficient IFN-mediated antiviral protection against influenza A and hepatitis C viruses. The Sin3a complex therefore acts as a context-dependent ISGF3/STAT3 transcriptional switch.
- Subjects :
- STAT3 Transcription Factor
Chromatin Immunoprecipitation
Blotting, Western
Hepacivirus
Real-Time Polymerase Chain Reaction
Cell Line
Mediator
Dogs
Animals
Humans
Immunoprecipitation
Protein inhibitor of activated STAT
STAT1
STAT2
STAT3
Luciferases
DNA Primers
Regulation of gene expression
Multidisciplinary
Microscopy, Confocal
General transcription factor
biology
Acetylation
Biological Sciences
Virus Internalization
Flow Cytometry
Microarray Analysis
Molecular biology
Interferon-Stimulated Gene Factor 3, gamma Subunit
Repressor Proteins
Sin3 Histone Deacetylase and Corepressor Complex
Gene Expression Regulation
Influenza A virus
biology.protein
RNA Interference
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1137b425472c0e4600e75bf57c00519a