Related Experiment Video
Updated: Jun 26, 2026

Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
Published on: November 30, 2018
ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation
Tiffany Hung1, Olivier Binda, Karen S Champagne
1Department of Biology, Stanford University, Stanford, CA 94305, USA.
Abstract:
Aberrations in chromatin dynamics play a fundamental role in tumorigenesis, yet relatively little is known of the molecular mechanisms linking histone lysine methylation to neoplastic disease. ING4 (Inhibitor of Growth 4) is a native subunit of an HBO1 histone acetyltransferase (HAT) complex and a tumor suppressor protein. Here we show a critical role for specific recognition of histone H3 trimethylated at lysine 4 (H3K4me3) by the ING4 PHD finger in mediating ING4 gene expression and tumor suppressor functions. The interaction between ING4 and H3K4me3 augments HBO1 acetylation activity on H3 tails and drives H3 acetylation at ING4 target promoters. Further, ING4 facilitates apoptosis in response to genotoxic stress and inhibits anchorage-independent cell growth, and these functions depend on ING4 interactions with H3K4me3. Together, our results demonstrate a mechanism for brokering crosstalk between H3K4 methylation and H3 acetylation and reveal a molecular link between chromatin modulation and tumor suppressor mechanisms.
Insights
The Inhibitor of Growth 4 (ING4) protein links histone H3 lysine 4 trimethylation (H3K4me3) to gene expression and tumor suppression. This interaction enhances HBO1 histone acetyltransferase activity, promoting anti-cancer functions.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- Chromatin dynamics are crucial in tumorigenesis, but the link between histone methylation and cancer is not fully understood.
- ING4 (Inhibitor of Growth 4) is a tumor suppressor and a component of the HBO1 histone acetyltransferase (HAT) complex.
Purpose of the Study:
- To investigate the role of ING4's interaction with histone H3 trimethylated at lysine 4 (H3K4me3) in gene expression and tumor suppression.
- To elucidate the molecular mechanisms connecting H3K4 methylation, H3 acetylation, and tumor suppressor functions.
Main Methods:
- Studied the interaction between the ING4 PHD finger and H3K4me3.
- Assessed the impact of this interaction on HBO1 HAT activity and H3 acetylation at target promoters.
- Evaluated ING4's role in apoptosis and anchorage-independent cell growth.
Main Results:
- ING4 specifically recognizes H3K4me3 via its PHD finger, which is critical for ING4's gene expression and tumor suppressor functions.
- ING4-H3K4me3 interaction enhances HBO1 HAT activity, leading to increased H3 acetylation at ING4 target promoters.
- ING4 facilitates apoptosis and inhibits anchorage-independent growth, dependent on H3K4me3 interaction.
Conclusions:
- Demonstrated a mechanism for crosstalk between H3K4 methylation and H3 acetylation.
- Revealed a molecular link between chromatin modulation, specifically H3K4me3 recognition by ING4, and tumor suppressor activities.
Related Concept Videos
Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Spreading of Chromatin Modifications
Writers
The writer is an enzyme that can...
Chromatin Modification in 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...
Heterochromatin
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Euchromatin
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...

