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

• Verfasst von: Icardi, Laura [VerfasserIn]
• Verfasst von: Boutros, Michael [VerfasserIn]
• Titel: The Sin3a repressor complex is a master regulator of STAT transcriptional activity
• Verf.angabe: Laura Icardi, 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, and Jan Tavernier
• E-Jahr: 2012
• Jahr: July 24, 2012
• Umfang: 6 S.
• Fussnoten: Gesehen am 20.11.2018
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2012
• Band/Heft Quelle: 109(2012), 30, Seite 12058-12063
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1206458109
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1583862153

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.