The Sin3a repressor complex is a master regulator of STAT transcriptional activity.

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.
Mesh Terms:
Acetylation, Animals, Blotting, Western, Cell Line, Chromatin Immunoprecipitation, DNA Primers, Dogs, Flow Cytometry, Gene Expression Regulation, Hepacivirus, Humans, Immunoprecipitation, Influenza A virus, Interferon-Stimulated Gene Factor 3, gamma Subunit, Luciferases, Microarray Analysis, Microscopy, Confocal, RNA Interference, Real-Time Polymerase Chain Reaction, Repressor Proteins, STAT3 Transcription Factor, Virus Internalization
Proc. Natl. Acad. Sci. U.S.A.
Date: Jul. 24, 2012
Download Curated Data For This Publication
157393
Switch View:
  • Interactions 3