Related Experiment Video
Updated: Jul 16, 2026
08:12
Global Level Quantification of Histone Post-Translational Modifications in a 3D Cell Culture Model of Hepatic Tissue
Published on: May 5, 2022
An Energy Model Based on Molecular Structure for Predicting Histone Modification Levels at lncRNA Promoter Regions in
Menglan Li1, Yingli Chen1,2, Qianzhong Li1,2
1Inner Mongolia Autonomous Region Key Laboratory of Biophysics and Bioinformatics, School of Physical Science and Technology, Inner Mongolia University, Hohhot 010021, China.
International Journal of Molecular Sciences
|July 15, 2026
Summary
This study introduces a novel computational model for analyzing histone modifications in hepatocellular carcinoma (HepG2) by examining DNA sequence features. The findings reveal a strong link between local DNA structure energy and histone modification patterns.
Area of Science:
- Molecular Biology
- Computational Biology
- Genomics
- Cancer Research
Background:
- Aberrant histone modifications in hepatocellular carcinoma (HepG2) are linked to long non-coding RNA (lncRNA) expression.
- Existing computational models for histone modifications lack physical interpretability at specific promoter regions.
- Understanding these modifications is crucial for deciphering gene regulation in cancer.
Purpose of the Study:
- To develop a physically interpretable computational model for histone modification analysis.
- To investigate the relationship between DNA sequence composition and histone modification states.
- To establish a quantitative link between local DNA structure energy and epigenetic modifications.
Main Methods:
- Developed a position-specific statistical scoring model utilizing adjacent and next-adjacent nucleotide frequencies.
- Trained two independent, position-specific matrices for increased and decreased modification states within 600 bp promoter windows.
- Employed ten-fold cross-validation to assess classification performance based on energy differences.
Main Results:
- The model demonstrated excellent classification performance in distinguishing between increased and decreased histone modification states.
- Significant energy differences were observed between DNA sequences associated with distinct histone modification signals.
- A strong correlation was identified between the total energy of local DNA structures and histone modification signals.
Conclusions:
- The developed model provides a physically interpretable approach to analyzing histone modifications.
- Local DNA structural energy is a significant determinant of histone modification patterns in HepG2 cells.
- This finding offers new insights into the epigenetic regulation of gene expression in hepatocellular carcinoma.
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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,...
Acetylation
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02:32Histone 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
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Acetylation
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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
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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...
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