scholarly journals Impairment of Interferon-Induced IRF-7 Gene Expression due to Inhibition of ISGF3 Formation by Trichostatin A

2003 ◽  
Vol 77 (12) ◽  
pp. 7113-7119 ◽  
Author(s):  
Pierre Génin ◽  
Pierre Morin ◽  
Ahmet Civas
Keyword(s):  
Gene Expression ◽  
Trichostatin A ◽  
Nuclear Accumulation ◽  
Signal Transducer ◽  
Interferon Stimulated Genes ◽  
Deacetylase Inhibitor ◽  
Dependent Inhibition ◽  
Infected Cells ◽  
And Function ◽  
Amplification Cascade

ABSTRACT Two members of the signal transducer and activator of transcription family, STAT1 and STAT2, form, together with interferon regulatory factor 9 (IRF-9), the ISGF3 complex that activates the expression of the interferon-stimulated genes (ISG). The ISGF3 complex also participates in the virus-induced alpha/beta interferon (IFN-α/β) gene amplification cascade by up-regulating IRF-7 gene expression. Here, we show that treatment of cells with trichostatin A (TSA), a deacetylase inhibitor, inhibits the virus-induced activation of IFN-α/β promoters and dramatically reduces the ability of different ISG promoters to respond to IFN stimulation. Impairment of IFN-α/β and ISG expression by TSA in infected cells is due to the blockage of interferon-stimulated ISGF3 complex formation, which leads to the abolition of IRF-7 gene expression. We also show that the TSA-dependent inhibition of ISGF3 is related to impaired nuclear accumulation of STAT2. Our data suggest that an acetylation/deacetylation mechanism participates in the regulation of cellular distribution and function of STAT2 in IFN-α/β signaling.

Azacitidine, as a DNMT Inhibitor Decreases hTERT Gene Expression and Telomerase Activity More Effective Compared with HDAC Inhibitor in Human Head and Neck Squamous Cell Carcinoma Cell Lines

2020 ◽  
Vol 14 (1) ◽  
pp. 60-67
Author(s):  
Sepideh Atri ◽  
Nikoo Nasoohi ◽  
Mahshid Hodjat
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Trichostatin A ◽  
Telomerase Activity ◽  
Htert Gene ◽  
Deacetylase Inhibitor

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most fatal malignancies worldwide and despite using various therapeutic strategies for the treatment of HNSCC, the surveillance rate is low. Telomerase has been remarked as the primary targets in cancer therapy. Considering the key regulatory role of epigenetic mechanisms in controlling genome expression, the present study aimed to investigate the effects of two epigenetic modulators, a DNA methylation inhibitor and a histone deacetylase inhibitor on cell migration, proliferation, hTERT gene expression, and telomerase activity in HNSCC cell lines. Methods: Human HNSCC cell lines were treated with Azacitidine and Trichostatin A to investigate their effects on telomerase gene expression and activity. Cell viability, migration, hTERT gene expression, and telomerase activity were studied using MTT colorimetric assay, scratch wound assay, qRT-PCR, and TRAP assay, respectively. Results: Azacitidine at concentrations of ≤1μM and Trichostatin A at 0.1 to 0.3nM concentrations significantly decreased FaDu and Cal-27 cells migration. The results showed that Azacitidine significantly decreased hTERT gene expression and telomerase activity in FaDu and Cal-27 cell lines. However, there were no significant changes in hTERT gene expression at different concentrations of Trichostatin A in both cell lines. Trichostatin A treatment affected telomerase activity at the high dose of 0.3 nM Trichostatin A. Conclusion: The findings revealed that unlike histone deacetylase inhibitor, Azacitidine as an inhibitor of DNA methylation decreases telomerase expression in HNSCC cells. This might suggest the potential role of DNA methyltransferase inhibitors in telomerase-based therapeutic approaches in squamous cell carcinoma.

scholarly journals Epigenetic Induction of Definitive and Pancreatic Endoderm Cell Fate in Human Fibroblasts

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Rangarajan Sambathkumar ◽  
Eric Kalo ◽  
Rob Van Rossom ◽  
Marijke M. Faas ◽  
Paul de Vos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Chromatin Remodeling ◽  
Dna Methyltransferase ◽  
Epigenetic Modification ◽  
Trichostatin A ◽  
Human Fibroblasts ◽  
Marker Genes ◽  
Deacetylase Inhibitor ◽  
Affect Gene Expression

Reprogramming can occur by the introduction of key transcription factors (TFs) as well as by epigenetic changes. We demonstrated that histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) combined with a chromatin remodeling medium (CRM) induced expression of a number of definitive endoderm and early and late pancreatic marker genes. When CRM was omitted, endoderm/pancreatic marker genes were not induced. Furthermore, treatment with DNA methyltransferase inhibitor (DNMTi) 5-azacytidine (5AZA) CRM did not affect gene expression changes, and when 5AZA was combined with TSA, no further increase in gene expression of endoderm, pancreatic endoderm, and endocrine markers was seen over levels induced with TSA alone. Interestingly, TSA-CRM did not affect expression of pluripotency and hepatocyte genes but induced some mesoderm transcripts. Upon removal of TSA-CRM, the endoderm/pancreatic gene expression profile returned to baseline. Our findings underscore the role epigenetic modification in transdifferentiation of one somatic cell into another. However, full reprogramming of fibroblasts to β-cells will require combination of this approach with TF overexpression and/or culture of the partially reprogrammed cells under β-cell specific conditions.

scholarly journals Rotavirus Antagonizes Cellular Antiviral Responses by Inhibiting the Nuclear Accumulation of STAT1, STAT2, and NF-κB

2009 ◽  
Vol 83 (10) ◽  
pp. 4942-4951 ◽  
Author(s):  
Gavan Holloway ◽  
Thanhmai T. Truong ◽  
Barbara S. Coulson
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Rna Virus ◽  
Host Responses ◽  
Nuclear Accumulation ◽  
Type I ◽  
Nonstructural Proteins ◽  
Necrosis Factor Alpha ◽  
Intracellular Expression ◽  
Infected Cells

ABSTRACT A vital arm of the innate immune response to viral infection is the induction and subsequent antiviral effects of interferon (IFN). Rotavirus reduces type I IFN induction in infected cells by the degradation of IFN regulatory factors. Here, we show that the monkey rotavirus RRV and human rotavirus Wa also block gene expression induced by type I and II IFNs through a mechanism allowing signal transducer and activator of transcription 1 (STAT1) and STAT2 activation but preventing their nuclear accumulation. In infected cells, this may allow rotavirus to block the antiviral actions of IFN produced early in infection or by activated immune cells. As the intracellular expression of rotavirus nonstructural proteins NSP1, NSP3, and NSP4 individually did not inhibit IFN-stimulated gene expression, their involvement in this process is unlikely. RRV and Wa rotaviruses also prevented the tumor necrosis factor alpha-stimulated nuclear accumulation of NF-κB and NF-κB-driven gene expression. In addition, NF-κB was activated by rotavirus infection, confirming earlier findings by others. As NF-κB is important for the induction of IFN and other cytokines during viral infection, this suggests that rotavirus prevents cellular transcription as a means to evade host responses. To our knowledge, this is the first report of the use of this strategy by a double-stranded RNA virus.

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