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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 and Geert Leroux-Roels UGent, et al. (2012) PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 109(30). p.12058-12063
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
DEACETYLASE ACTIVITY, ACUTE-PHASE RESPONSE, CELLS, PROTEINS, ACETYLATION, GROWTH, ACTIVATION, GENE-EXPRESSION, SIGNAL TRANSDUCER, INTERFERON-GAMMA
journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Proc. Natl. Acad. Sci. USA
volume
109
issue
30
pages
12058 - 12063
Web of Science type
Article
Web of Science id
000306992700042
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
9.737 (2012)
JCR rank
4/56 (2012)
JCR quartile
1 (2012)
ISSN
0027-8424
DOI
10.1073/pnas.1206458109
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
project
Ghent researchers on unfolded proteins in inflammatory disease (GROUP-ID)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2983518
handle
http://hdl.handle.net/1854/LU-2983518
date created
2012-09-07 15:48:27
date last changed
2014-05-12 11:00:59
@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},
  keyword      = {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},
}

Chicago
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.
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.
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.
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.