Format

Send to

Choose Destination

Links from GEO DataSets

See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12058-63. doi: 10.1073/pnas.1206458109. Epub 2012 Jul 10.

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

Author information

  • 1Department of Medical Protein Research, Vlaams Instituut voor Biotechnologie, 9000 Ghent, Belgium.

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.

PMID:
22783022
PMCID:
PMC3409767
DOI:
10.1073/pnas.1206458109
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center