Related Experiment Video

Updated: Aug 29, 2026

Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark
10:09

Isolation and Cultivation of Neural Progenitors Followed by Chromatin-Immunoprecipitation of Histone 3 Lysine 79 Dimethylation Mark

Published on: January 26, 2018

Resetting the histone code at CDKN2A in HNSCC by inhibition of DNA methylation

Madelene M Coombes1, Katrina L Briggs, James R Bone

  • 1Department of Biochemistry and Molecular Biology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.

Oncogene
|December 5, 2003
PubMed

Insights

DNA methylation silences the p16 tumor suppressor in head and neck cancer. Combining DNA-demethylating agents with HDAC inhibitors reactivates p16, offering potential therapeutic strategies for HNSCC.

Area of Science:

  • Oncology
  • Epigenetics
  • Cancer Biology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer linked to genetic and epigenetic alterations.
  • Inactivation of the CDKN2A gene, encoding the p16 tumor suppressor, via DNA methylation is a key event in HNSCC.
  • Reactivating tumor suppressor genes using epigenetic modifiers shows therapeutic potential in various cancers.

Purpose of the Study:

  • To investigate the potential of DNA-demethylating agents and histone deacetylase (HDAC) inhibitors to reactivate p16 in HNSCC cells.
  • To determine the synergistic effects of sequential treatment with 5-aza-2'deoxycytidine (5-aza-dC) and trichostatin A (TSA) on CDKN2A expression.

Main Methods:

  • Treatment of Tu159 HNSCC cells with 5-aza-dC and/or TSA.
  • Analysis of CDKN2A expression, histone H3 acetylation, and histone H3 methylation (H3-K9 and H3-K4) at the CDKN2A promoter.
  • Assessment of global H3-K9 methylation levels.

Main Results:

  • 5-aza-dC treatment increased CDKN2A expression and H3 acetylation at the gene.
  • TSA alone did not reactivate CDKN2A, but sequential treatment with 5-aza-dC and TSA synergistically reactivated CDKN2A.
  • CDKN2A silencing correlated with increased H3-K9 methylation and decreased H3-K4 methylation; 5-aza-dC reduced global H3-K9 methylation.

Conclusions:

  • DNA methylation is a primary mechanism for silencing CDKN2A in Tu159 HNSCC cells.
  • Combined epigenetic therapy (5-aza-dC and TSA) can synergistically reactivate the silenced CDKN2A tumor suppressor.
  • Modulating DNA methylation can influence histone modifications, potentially resetting the epigenetic landscape in cancer cells.

More Related Videos

Extraction of Histones from Clinical Specimens for Epigenetic Profiling by Mass Spectrometry10:54

Extraction of Histones from Clinical Specimens for Epigenetic Profiling by Mass Spectrometry

Published on: November 21, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers10:28

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

Epigenetic Regulation

Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...