Related Experiment Video

Updated: May 18, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
09:11

Assays for Validating Histone Acetyltransferase Inhibitors

Published on: August 6, 2020

Interferon regulatory factor-8 is important for histone deacetylase inhibitor-mediated antitumor activity

Debarati Banik1, A Nazmul H Khan, Even Walseng

  • 1Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.

Plos One
|October 3, 2012
PubMed

Insights

Histone deacetylase inhibitors (HDACi) can target cancer cells. This study shows interferon regulatory factor (IRF)-8 is crucial for HDACi to induce tumor cell death, suggesting IRF-8 status predicts treatment response.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Epigenetic alterations in cancer are reversible, driving interest in epigenetic modifiers for cancer therapy.
  • Histone deacetylase inhibitors (HDACi) are a promising class of anti-neoplastic agents, but their molecular targets remain unclear.
  • Interferon regulatory factor (IRF)-8, a known apoptosis regulator, also influences Fas-mediated killing and is epigenetically repressed in tumors.

Purpose of the Study:

  • To investigate the hypothesis that interferon regulatory factor (IRF)-8 expression is essential for the anti-tumor effects of HDAC inhibitors.
  • To explore the molecular mechanisms by which HDAC inhibitors impact IRF-8 expression and function in cancer cells.

Main Methods:

  • Utilized a preclinical tumor model treated with the pan-HDAC inhibitor Trichostatin A (TSA), alone and in combination with Interferon-gamma (IFN-γ).
  • Assessed IRF-8 expression, promoter activity, and its role in Fas-mediated cell death in vitro.
  • Evaluated the impact of IRF-8 deficiency on tumor cell susceptibility to HDACi-mediated anti-tumor activity in vivo.

Main Results:

  • Trichostatin A (TSA) treatment, particularly with IFN-γ, significantly enhanced IRF-8 expression and Fas-mediated tumor cell death in vitro.
  • TSA increased IRF-8 promoter activity through a STAT1-dependent pathway.
  • Tumor cells lacking IRF-8 exhibited reduced susceptibility to Fas-mediated killing and diminished response to HDACi treatment in vivo.

Conclusions:

  • Interferon regulatory factor (IRF)-8 expression is a critical determinant of response to HDAC inhibitor-based cancer therapy.
  • IRF-8 status may represent a novel molecular biomarker for predicting efficacy of HDACi treatments.
  • Targeting or understanding IRF-8 could enhance the effectiveness of epigenetic therapies in cancer treatment.

More Related Videos

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF311:44

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization08:57

Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization

Published on: October 6, 2019

Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification02:32

Histone Modification

The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...