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Opposed regulation of type I IFN-induced STAT3 and ISGF3 transcriptional activities by histone deacetylases (HDACS) 1 and 2

Laura Icardi, Sam Lievens UGent, Raffaele Mori UGent, Julie Piessevaux UGent, Lode De Cauwer, Karolien De Bosscher UGent and Jan Tavernier UGent (2012) FASEB JOURNAL. 26(1). p.240-249
abstract
The antiviral and antiproliferative responses mediated by type I interferons (IFNs) depend on JAK/STAT signaling and ISGF3 (STAT1:STAT2:IRF9)-dependent transcription. In addition, type I IFNs stimulate STAT3 activation in many cell types, an event generally associated with cell cycle progression, survival, and proliferation. To gather more insight into this functionally contradictive phenomenon, we studied the regulation of STAT3 transcriptional activity upon type I IFN treatment. We show that IFN alpha 2 stimulation strongly induces STAT3 phosphorylation, nuclear translocation, and promoter binding, yet the activation of transcription of a STAT3-dependent reporter and endogenous genes, such as SOCS3 and c-FOS, is impaired. Simultaneous treatment with IFN alpha 2 and trichostatin A, as well as combined HDAC1/HDAC2 silencing, restores STAT3-dependent reporter gene and endogenous gene expression, strongly suggesting that HDAC1 and HDAC2 are directly involved in repressing IFN alpha 2-activated STAT3. Of note, single silencing of only one of the two HDACs does not lead to enhanced STAT3 activity, supporting a functional redundancy between these two enzymes. In sharp contrast, HDAC1 and HDAC2 activities are required for ISGF3-dependent gene expression. We conclude that HDAC1 and HDAC2 differentially modulate STAT activity in response to IFN alpha 2: while they are required for the induction of ISGF3-responsive genes, they impair the transcription of STAT3-dependent genes.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IL-6, RESPONSES, BETA, GROWTH, ACETYLATION, RECEPTOR, ACTIVATION, INTERFERON-GAMMA, GENE-EXPRESSION, NEGATIVE REGULATION, interferon-stimulated genes, TSA, trichostatin A, interferon signaling
journal title
FASEB JOURNAL
Faseb J.
volume
26
issue
1
pages
240 - 249
Web of Science type
Article
Web of Science id
000299202200025
JCR category
BIOLOGY
JCR impact factor
5.704 (2012)
JCR rank
7/83 (2012)
JCR quartile
1 (2012)
ISSN
0892-6638
DOI
10.1096/fj.11-191122
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2055166
handle
http://hdl.handle.net/1854/LU-2055166
date created
2012-03-01 11:50:54
date last changed
2016-12-19 15:44:51
@article{2055166,
  abstract     = {The antiviral and antiproliferative responses mediated by type I interferons (IFNs) depend on JAK/STAT signaling and ISGF3 (STAT1:STAT2:IRF9)-dependent transcription. In addition, type I IFNs stimulate STAT3 activation in many cell types, an event generally associated with cell cycle progression, survival, and proliferation. To gather more insight into this functionally contradictive phenomenon, we studied the regulation of STAT3 transcriptional activity upon type I IFN treatment. We show that IFN alpha 2 stimulation strongly induces STAT3 phosphorylation, nuclear translocation, and promoter binding, yet the activation of transcription of a STAT3-dependent reporter and endogenous genes, such as SOCS3 and c-FOS, is impaired. Simultaneous treatment with IFN alpha 2 and trichostatin A, as well as combined HDAC1/HDAC2 silencing, restores STAT3-dependent reporter gene and endogenous gene expression, strongly suggesting that HDAC1 and HDAC2 are directly involved in repressing IFN alpha 2-activated STAT3. Of note, single silencing of only one of the two HDACs does not lead to enhanced STAT3 activity, supporting a functional redundancy between these two enzymes. In sharp contrast, HDAC1 and HDAC2 activities are required for ISGF3-dependent gene expression. We conclude that HDAC1 and HDAC2 differentially modulate STAT activity in response to IFN alpha 2: while they are required for the induction of ISGF3-responsive genes, they impair the transcription of STAT3-dependent genes.},
  author       = {Icardi, Laura and Lievens, Sam and Mori, Raffaele and Piessevaux, Julie and De Cauwer, Lode and De Bosscher, Karolien and Tavernier, Jan},
  issn         = {0892-6638},
  journal      = {FASEB JOURNAL},
  keyword      = {IL-6,RESPONSES,BETA,GROWTH,ACETYLATION,RECEPTOR,ACTIVATION,INTERFERON-GAMMA,GENE-EXPRESSION,NEGATIVE REGULATION,interferon-stimulated genes,TSA,trichostatin A,interferon signaling},
  language     = {eng},
  number       = {1},
  pages        = {240--249},
  title        = {Opposed regulation of type I IFN-induced STAT3 and ISGF3 transcriptional activities by histone deacetylases (HDACS) 1 and 2},
  url          = {http://dx.doi.org/10.1096/fj.11-191122},
  volume       = {26},
  year         = {2012},
}

Chicago
Icardi, Laura, Sam Lievens, Raffaele Mori, Julie Piessevaux, Lode De Cauwer, Karolien De Bosscher, and Jan Tavernier. 2012. “Opposed Regulation of Type I IFN-induced STAT3 and ISGF3 Transcriptional Activities by Histone Deacetylases (HDACS) 1 and 2.” Faseb Journal 26 (1): 240–249.
APA
Icardi, L., Lievens, S., Mori, R., Piessevaux, J., De Cauwer, L., De Bosscher, K., & Tavernier, J. (2012). Opposed regulation of type I IFN-induced STAT3 and ISGF3 transcriptional activities by histone deacetylases (HDACS) 1 and 2. FASEB JOURNAL, 26(1), 240–249.
Vancouver
1.
Icardi L, Lievens S, Mori R, Piessevaux J, De Cauwer L, De Bosscher K, et al. Opposed regulation of type I IFN-induced STAT3 and ISGF3 transcriptional activities by histone deacetylases (HDACS) 1 and 2. FASEB JOURNAL. 2012;26(1):240–9.
MLA
Icardi, Laura, Sam Lievens, Raffaele Mori, et al. “Opposed Regulation of Type I IFN-induced STAT3 and ISGF3 Transcriptional Activities by Histone Deacetylases (HDACS) 1 and 2.” FASEB JOURNAL 26.1 (2012): 240–249. Print.