Related Experiment Video
Updated: Aug 11, 2026
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Hydrogen peroxide mediates higher order chromatin degradation
1Department of Neurobiology and Anatomy, West Virginia University School of Medicine, 4052 HSN, P O Box 9128, Morgantown, WV 26506-9128, USA.
Neurochemistry International
|November 8, 2002
Summary
Hydrogen peroxide (H2O2) specifically triggers higher-order chromatin degradation (HOCD) via cytoplasmic signaling pathways. This rapid HOCD response is observed across various cell types, not just glial cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- Oxidative stress is linked to neurodegeneration, but underlying mechanisms remain unclear.
- Hydrogen peroxide (H2O2) is a key mediator of oxidative stress.
- Previous work demonstrated H2O2 induces higher-order chromatin degradation (HOCD) via matrix attachment region (MAR) excision.
Purpose of the Study:
- To investigate the specificity of H2O2 in inducing HOCD.
- To elucidate the cellular pathways involved in H2O2-induced HOCD.
Main Methods:
- Rat glioma C6 cells were exposed to H2O2 and other oxidants.
- Genomic DNA fragmentation was assessed using field inversion gel electrophoresis (FIGE).
- S1 digestion was used to detect single-strand fragmentation.
Main Results:
- H2O2 rapidly induced HOCD within 30 minutes at concentrations as low as 5 μM.
- HOCD was largely reversible, suggesting efficient chromatin fragment rejoining.
- H2O2 did not induce HOCD in isolated nuclei, indicating indirect activation via cytoplasmic signaling.
- Synthetic peroxide (tBH) induced HOCD to a lesser extent than H2O2.
- Hypochlorite and nitric oxide generators did not induce rapid HOCD.
Conclusions:
- Rapid HOCD is specifically triggered by H2O2 signaling cascades, not oxidative stress generally.
- HOCD induction by H2O2 is a general cellular response observed in multiple rat and human cell lines.
- Findings suggest H2O2-induced HOCD may play a role in neurodegenerative processes.
Related Concept Videos
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:25Spreading of Chromatin Modifications
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
The writer is an enzyme that can...
Writers
The writer is an enzyme that can...
02:36Chromatin Immunoprecipitation- ChIP
Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
Types of ChIP
ChIP can be divided into two types - X-ChIP and N-ChIP. X-ChIP involves in vivo cross-linking of histones and regulatory proteins to DNA, fragmenting the DNA by sonication, and isolating the protein-DNA...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative 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...
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...
01:32Chromatin 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...
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...