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

Laura Icardi (UGent) , Raffaele Mori (UGent) , Viola Gesellchen (UGent) , Sven Eyckerman (UGent) , Lode De Cauwer (UGent) , Judith Verhelst (UGent) , Koen Vercauteren (UGent) , Xavier Saelens (UGent) , Philip Meuleman (UGent) , Geert Leroux-Roels (UGent) , et al.
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
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.
Keywords
DEACETYLASE ACTIVITY, ACUTE-PHASE RESPONSE, CELLS, PROTEINS, ACETYLATION, GROWTH, ACTIVATION, GENE-EXPRESSION, SIGNAL TRANSDUCER, INTERFERON-GAMMA

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MLA
Icardi, Laura, Raffaele Mori, Viola Gesellchen, et al. “The Sin3a Repressor Complex Is a Master Regulator of STAT Transcriptional Activity.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 109.30 (2012): 12058–12063. Print.
APA
Icardi, L., Mori, R., Gesellchen, V., Eyckerman, S., De Cauwer, L., Verhelst, J., Vercauteren, K., et al. (2012). The Sin3a repressor complex is a master regulator of STAT transcriptional activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(30), 12058–12063.
Chicago author-date
Icardi, Laura, Raffaele Mori, Viola Gesellchen, Sven Eyckerman, Lode De Cauwer, Judith Verhelst, Koen Vercauteren, et al. 2012. “The Sin3a Repressor Complex Is a Master Regulator of STAT Transcriptional Activity.” Proceedings of the National Academy of Sciences of the United States of America 109 (30): 12058–12063.
Chicago author-date (all authors)
Icardi, Laura, 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. 2012. “The Sin3a Repressor Complex Is a Master Regulator of STAT Transcriptional Activity.” Proceedings of the National Academy of Sciences of the United States of America 109 (30): 12058–12063.
Vancouver
1.
Icardi L, Mori R, Gesellchen V, Eyckerman S, De Cauwer L, Verhelst J, et al. The Sin3a repressor complex is a master regulator of STAT transcriptional activity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2012;109(30):12058–63.
IEEE
[1]
L. Icardi et al., “The Sin3a repressor complex is a master regulator of STAT transcriptional activity,” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 109, no. 30, pp. 12058–12063, 2012.
@article{2983518,
  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.},
  author       = {Icardi, Laura and Mori, Raffaele and Gesellchen, Viola and Eyckerman, Sven and De Cauwer, Lode and Verhelst, Judith and Vercauteren, Koen and Saelens, Xavier and Meuleman, Philip and Leroux-Roels, Geert and De Bosscher, Karolien and Boutros, Michael and Tavernier, Jan},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {DEACETYLASE ACTIVITY,ACUTE-PHASE RESPONSE,CELLS,PROTEINS,ACETYLATION,GROWTH,ACTIVATION,GENE-EXPRESSION,SIGNAL TRANSDUCER,INTERFERON-GAMMA},
  language     = {eng},
  number       = {30},
  pages        = {12058--12063},
  title        = {The Sin3a repressor complex is a master regulator of STAT transcriptional activity},
  url          = {http://dx.doi.org/10.1073/pnas.1206458109},
  volume       = {109},
  year         = {2012},
}

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