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

(2012) FASEB JOURNAL. 26(1). p.240-249
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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.
Keywords
IL-6, RESPONSES, BETA, GROWTH, ACETYLATION, RECEPTOR, ACTIVATION, INTERFERON-GAMMA, GENE-EXPRESSION, NEGATIVE REGULATION, interferon-stimulated genes, TSA, trichostatin A, interferon signaling

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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.
@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},
}

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