| Literature DB >> 22783022 |
Laura Icardi1, Raffaele Mori, Viola Gesellchen, Sven Eyckerman, Lode De Cauwer, Judith Verhelst, Koen Vercauteren, Xavier Saelens, Philip Meuleman, Geert Leroux-Roels, Karolien De Bosscher, Michael Boutros, Jan Tavernier.
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.Entities:
Mesh：
Substances：
Year: 2012 PMID： 22783022 PMCID： PMC3409767 DOI： 10.1073/pnas.1206458109
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205